Automated Metabolic Network Reconstruction by Exploiting Functional Homology

Master’s Thesis

Automated metabolic network reconstruction by exploiting functional homology

Thesis Committee: Prof.dr.ir. M.J.T. Reinders Dr.ir. D. de Ridder Dr. M.J.L. de Groot Dr.ir. G. Lequeux Dr. C. Picioreaunu Dr. L. Wu

Author Tisha Melia Email [email protected] Student number 1388363 Thesis supervisor Dr.ir. D. de Ridder Dr. M.J.L. de Groot Date November 27, 2009

Information and T Communication Theory Group [I,C) Preface

This thesis report serves as the documentation of a research project conducted on the topic of metabolic networks reconstruction in the Information and Com- munication Theory (ICT) group, Delft University of Technology. The document consists of four parts: a paper, a supplementary material, a work document, and a collection of graphs depicting a part of the Saccharomyces cerevisiae reconstructed metabolic network (based enriched model pathways at 28% false positive rate of one-step predictions).

This research was done as a partial fulﬁllment for a master degree in Media and Knowledge Engineering (Bioinformatics track) and supervised by Dr.ir. D. de Ridder and Dr. M.J.L. de Groot.

The full metabolic network graphs is available upon request.

Acknowledgement

For the completion of this thesis, I would like to thank both of my supervisors who have guided me and put up with me during the entire course of the project. I realize the latter is a harder task to tackle than the former. Two years ago, I have never heard of the term m-RNA; and now at the end of the two years, I am able to reconstruct metabolic networks. This is due to the persistence of these two tall Dutch men. Thank you very much.

Although a lot of people have supported me throughout this project, I would like to distinguish a few of them: former and current housemates (Taya, Emily, and Uni Rini); friends that are always there no matter what (Enny, Zahira, Zaiyan, Innocent, Taraz, and Ruske); friends that always allow me to crash in their apartment (Hanim and Winnie); and the ”glass room” master students whose help ranging from translating all my Dutch mails, immersing me into the wonder of Dutch fast food, to biking together to Scheveningen (Jeroen, Bas, Joao, Jelle, Rostand, Patrick, Vasili, Baqir and Raul).

The last but not least, I would like to thank my family for their full support, despite all odds.

Delft, November 13, 2009 Tisha Melia

1 Vol. 00 no. 00 2009 BIOINFORMATICS Pages 1–10

Automated metabolic network reconstruction by exploiting functional homology Tisha Melia TU Delft

ABSTRACT comparing the novel genome to the sequences of known genes in Motivation: As the metabolic network reconstruction process via a well-curated database (e.g. KEGG GENES). Each gene listing is manual curation proves to be a tedious process, the need for an usually accompanied by the details of the enzyme it encodes (e.g. automated reconstruction tool becomes imminent. There has been enzyme name, EC number, accession number of its amino acid previous attempts to automate metabolic network reconstruction. sequence, etc). EC Number is a classification scheme to categorize These existing approaches rely on sequence similarity to infer enzymes based on the type of chemical reactions they catalyze. functions. Consequently, they fail to identify functions in the absence These enzymes are then organized into pathways by finding its EC of sequence similarity or when sequences are heterogeneous. We number in existing pathway charts (e.g. KEGG pathways). The propose a new method to automate metabolic network reconstruction EC number can also be used to find the stoichiometry (e.g. using that combines sequence similarity information and the likelihood of ExPASy proteomics database [8]). This results in a list of reactions a certain enzyme to catalyze an enzymatic transformation. At the that are possible in the organism of interest. Aside from using online end, we combine both sequence homology and functional homology databases, metabolic reconstruction processes also use information information to automatically reconstruct metabolic network. derived from biochemistry textbooks and publications, extracting Results: We are able to achieve more correct predictions than pure the current state of the art of metabolic reactions. The tedious sequence homology-based methods at the expense of increased process of piecing together the information from multiple sources false positive rate. Additionally, we develop a mechanism to becomes a bottleneck in reconstructing metabolic networks. As a detect isoenzymes and protein complexes during the reconstruction consequence, the reconstruction of metabolic networks lags behind process. compared to the recent increase in genome sequencing. There is a clear need for a method to further automate the metabolic network reconstruction process.

1 INTRODUCTION Several approaches to automatically reconstruct metabolic networks Knowing the metabolism of an organism is key to uncovering have been proposed [12][16][18]. These methods base their all of the biochemical functions it can potentially perform. predictions on sequence homology, a measure of similarity of A metabolic network catalogs all reactions that take place in newly annotated genes to known enzyme-coding genes. Thus they an organism. These reactions are organized into pathways.A fail to assign functions to genes or proteins that have limited pathway typically corresponds to a single metabolic function (i.e. sequence resemblance to their orthologous counterparts. It has been biosynthesis or degradation of a certain substance). Knowing the reported that sequence homology-based approaches are not able to full extent of an organism’s metabolic networks plays an important assign functions to 31-80% of genes [14]. Therefore, there is a role in metabolic engineering, rational genetic alteration of an need for a metabolic network reconstruction method that does not organism to produce substrates that have commercial or research entirely base its prediction on sequence similarity. In this work, we significance, or to inhibit production of harmful byproducts. propose a method that combines sequence homology and functional Other applications of metabolic networks include improving the information of enzymes. For the functional information, we use the details of genome annotation, uncovering the metabolism of newly MaRIboES system [3], which rates the likelihood of an enzyme sequenced organisms through comparative analysis, and finding to interact with a compound and predicts the resulting metabolic alternative drug targets. Two major database; MetaCyc [13] and product. We use this information as evidence to add reactions into Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways metabolic networks reconstructed based on sequence homology. [11], record known metabolic networks found in various organisms. In essence, we refine the concept of enzyme homology: not only These metabolic networks were collected mainly through manual, similarity in sequence, but also similarity in function. literature-based curation. Our approach is based on work performed earlier on model Recently, a large number of genome-wide metabolic networks have pathways [18]. Briefly, in this method each reaction is represented become available. The network reconstruction processes are usually by the set of sequences of all enzymes known to catalyze conducted in a partially-automated fashion, requiring iterative it. Reconstruction is then performed by looking for enzymes decision-making processes that can easily take up to one man- homologous to any of the sequences (i.e. using BLAST [1]), or by year to finish [6]. The reconstruction process usually begins by training a profile HMM on this set. We found that the sensitivity of looking for genes in a newly sequenced genome. It is done by

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Fig. 1. Overview of the proposed approach. Boxes in yellow indicate the training phase, boxes in green the test phase, whereas the baseline approach is denoted in orange. The numbering is used in Section 2 to discuss the individual components. Further implementation details can be found in the supplementary material.

HMM profiles in detecting orthologous proteins is hampered by the A to compound B, the annotated path may be only one of them. heterogeneity of the sequence set. We extended the reconstruction The other path is a candidate for an alternative pathway. Showing method by clustering the sequences set based on its similarity and the possibility of alternative reactions may be useful in the situation then training a profile HMM per cluster. This allows us to identify where the complete knowledge of a metabolic network is necessary. isoenzymes and protein complexes. An example model pathway is that of the tricarboxylic acid cycle (TCA cycle) in Figure 2. This particular model pathway is the To validate our proposed algorithm, we apply it to reconstruct union of six pathways, each of which is found in a different Saccharomyces cerevisiae metabolic network. Although our method set of species. The TCA cycle pathway is found in Azotobacter is able to find more correct predictions, to improve annotation, and vinelandii and Escherichia coli K-12 substr. MG1655; variation to suggest possible isoenzymes, we also increase the number of false I in Mycobacterium tuberculosis, Mycobacterium smegmatis, and positive predictions. Hence, there is a tradeoff between the degree Mycobacterium bovis; variation II in Helicobacter pylori 26695; of completeness and the quality of the reconstructed metabolic variation III in Arabidopsis thaliana col, Glycine max, Homo networks. This suggests a role for application of our system in cases sapiens, Vigna radiata, and Saccharomyces cerevisiae; variation where a higher sensitivity is required –than can be achieved using IV in Acidithiobacillus thiooxidans, Thiobacillus thioparus, sequence homology alone– at the cost of a lower enzyme specificity. Synechocystis sp. PCC 6308, Cyanobium gracile PCC 6307, and Synechococcus elongatus PCC 7942; and the glyoxylate cycle pathway is found in Arabidopsis thaliana col and Escherichia coli K-12 substr. MG1655. Various colored edges denote the contribution of each pathway instance towards the model pathway.

2 OVERVIEW OF THE SYSTEM We use model pathways as templates for our prediction algorithm. For each reaction in each model pathway, we gather the amino acid The proposed method consists of two phases: a training and sequences of all enzymes known to catalyze it (based on their EC testing/application phase (Figure 1). In the training phase, we numbers). We denote these amino acid sequences as our training set; construct pathways that will serve as the prediction template and each reaction has its own training set. We only consider reactions compute all the necessary parameters to optimize our prediction which receive a complete EC number in our prediction algorithm algorithm. In the testing phase, we use the parameters learned during (i.e. having all four digits of the EC number). This training set the training phase to reconstruct metabolic networks. is used to find the homologous enzyme that catalyzes it in the proteome of the reconstructed organism (Figure 1, Box 6). We As a starting point of our prediction, we use the concept of model employ two methods to find homologous enzyme: BLAST and pathways, introduced by Pireddu et al. [18] (Figure 1, Box 1). A profile HMM (Figure 1, Box 5). The use of both methods are model pathway is the union of all organism pathways known for a complementary to each other in finding homologous enzyme, as particular type of pathway (e.g. glycolysis, fatty acid biosynthesis, discussed in Section 3.4 and supplementary material. etc). Therefore, a model pathway contains all variation found across organisms for a particular pathway. There are two main Finding homologous enzymes is challenging, as the training set is reasons to use model pathways as the basis of our prediction rather often comprised of heterogeneous sequences. This heterogeneity than a single pathway instance. First, model pathways account for is either due to non-homologous enzymes catalyzing the same variations that exist in all organisms. Given a new organism to reaction or protein complexes receiving the same EC number. As an reconstruct, only using a single pathway instance decreases the illustration, for the enzyme alcohol dehydrogenase (EC 1.1.1.1), we chance that the true pathway of the new organism has the same find there are 367 unique UniProt accession numbers annotated with structure with the pathway instance. Using a model pathway, the this EC number. Additionally, PROSITE lists three types of alcohol new organism may be evolutionary related to one of the organisms dehydrogenase currently known and indicates that most species that contributes a pathway to the model pathway. Therefore, we have have multiple alcohol dehydrogenase isoenzymes [10]. In building a higher chance to predict the right pathway given a new organism our prediction tool, we first cluster (group) these sequences based on to reconstruct. Second, model pathways may reveal alternative mutual similarity, so that clusters are more homogeneous, making it pathways. In case we predict more than one path from compound

2 Tools We use the following tools as components to build our prediction software. For ﬁnding homologous proteins, we use BLAST version 2.2.19; for computing multiple alignment, we use CLUSTALW2 version 2.0.10 ([21]); for building HMM models, we use HMMER version 2.3.2 ([5]); for computing global pairwise alignment to build our distance matrix, we use EMBOSS version 6.1.0 ([19]). Parameters are set to the recommended values provided by each respective tool; namely gap open penalty = 11, gap extension penalty = 1, and substitution matrix = BLOSUM62 for BLAST; gap open penalty = 10, gap extension penalty = 0.2, substitution matrix = GONNET 250, ending gap penalty = -1, and gap distance penalty = 4 for CLUSTALW2; gap open penalty = 10, gap extension penalty = 0.5 and substitution matrix = BLOSUM62 for EMBOSS. 3.2 Base model pathways We use curated pathways from various organisms available through MetaCyc for constructing model pathways. MetaCyc has organized these pathways Fig. 2. The model pathway for TCA variants, a union of six pathways. Each into 347 groups based on similarity in function. We use this data to set up as colour denotes a variant of the TCA pathway found in different organisms. many model pathways across all organisms.

To formally introduce the model pathway, let r(c1,c2,a) denote reaction r that transforms compound c1 into compound c2, catalyzed by enzyme a. If easier to generalize sequence homology using profile HMMs. For a pathway m contains the reaction r , r , r and every reaction, we calculate the optimum number of clusters within 1 (c1,c2,a) (c2,c3,b) (c3,c4,c) a pathway m2 contains the reaction r(c1,c2,d), r(c2,c3,b), r(c3,c5,e), then each training set (Figure 1, Box 4). This is the first contribution of the model pathway M is defined as: this paper M = m1 m2 ∪ Our second contribution is to enrich our model pathways with = r(c ,c ,a), r(c ,c ,d), r(c ,c ,b), r(c ,c ,c), r(c ,c ,e) reactions that could not be inferred via sequence similarity (Figure 1 2 1 2 2 3 3 4 3 5 1, Box 3), using the MaRIboES system to predict functional 3.3 Enriched model pathways homology (Figure 1, Box 2). These newly added reactions are either 3.3.1 One-step prediction We enrich our model pathways with single reactions (one-step predictions) or alternative paths between predictions by MaRIboES, a system developed by de Groot et al. [3]. two compounds (multi-step predictions). A final contribution is a MaRIboES is an algorithm that predicts the possibility of an enzymatic mechanism to rank and select these multi-step predictions (Figure transformation and its output compound, given an input compound. 1, Box 2, multi-step prediction). MaRIboES exploits the fact that many enzymes can catalyze reactions involving more compounds than the ones listed in curated databases. Enzyme aspecificities are modelled such that MaRIboES can rate the likelihood of a certain enzyme to catalyze a certain enzymatic transformation 3 MATERIALS AND METHODS involving a specific substrate.

3.1 Data For each EC number, MaRIboES models its enzymatic transformation(s) Training Data by extracting the-so-called RN patterns from every reactant pairs of all We gathered 7940 reactions, 7719 compounds, and 1290 organism-specific reactions listed for that EC Number. RN patterns record the entire enzymatic pathways from MetaCyc version 13.0 (released on March 17, 2009). transformation undergone by a compound. An RN pattern consists of two Metacyc contains curated metabolic pathways from multiple organisms. The patterns: an RN pattern for the substrate (RNs-) and an RN pattern for the data is subject to manual curation and scientific literature checks. Additional product (RNp-). The RN pattern of a compound is calculated by aligning the information on proteins is derived from UniProt version 14.9 (released on molecules (drawn as graphs) of the substrate and the product. The alignment March 3, 2009). We only used the manually curated protein database of produces a matched region and an unmatched region. All atoms belonging to UniProt for the training data (UniProtKB/Swiss-Prot). The total number of the unmatched region are denoted as N atoms and all atoms that belong to the proteins used is 412,552. matched region and adjacent to an N atom are labelled as R atoms. Hence, an RN pattern records the full difference between a substrate and product. Testing Data It is possible for an enzyme to have multiple enzymatic transformations (i.e. Next to the protein set we use for training, we collected 7,537,442 amino multiple RN patterns). acid sequences from UniProtKB/TrEMBL version 14.9 (released on March 3, 2009). UniProtKB/TrEMBL contains the translations of all coding For each transformation pattern of a particular enzyme, MaRIboES finds sequences present in the EMBL/GenBank/DDBJ Nucleotide Sequence other compounds that possess the same RNs- or RNp- pattern. These Databases, as well as protein sequences found in literature or submitted to compounds are divided into two sets: positive examples (compounds listed UniProtKB. We grouped these sequences based on the organism in which in BRENDA [2] to be catalyzed by the enzyme being considered) and they were found. This resulted in 196,190 groups of sequences. Each group negative examples (all others). Based on these examples, MaRIboES predicts contains a proteome (i.e. all protein sequences of a specific species of whether a new compound is likely to be converted by the enzyme. If the new a specific strain). These proteomes are used as the test data for finding compound is similar to the positive examples in terms of structural similarity homologous sequences, both in protein complex and isoenzyme detection (with respect to the closest positive example), stereo dissimilarity (with (Figure 1, Box 4) and metabolic network reconstruction of the organism of respect to the closest positive example), binary fingerprints, and discrete interest (Figure 1, Box 6). fingerprints, we expect it to be more likely to be converted by the enzyme.

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These predictions are performed by MaRIboES classifiers. A MaRIboES classifier outputs a posterior probability that reflects the likelihood of a certain compound to undergo a certain enzymatic transformation done by a specific enzyme. We use this posterior probability to determine which reactions to be added into our base model pathways: predictions which posterior probability is greater than α are considered as true. For further reference, we will refer to this as our α threshold.

Due to the difference in the specificity of the RN patterns of various enzymatic transformations, some enzymatic transformations produce more results than others. MaRIboES employ significance tests as another way to filter prediction results. Prediction results are ordered based on their posterior probabilities and are labelled either as ’positive’ or ’negative’. A prediction receives the label ’positive’ if the prediction is found back in the list of reactions in BRENDA; if not, the prediction receives the label ’negative’. The null hypothesis is that the top n predictions are not enriched with true positives. MaRIboES starts at n=1 and keeps increasing the number of predictions included in the top n until the probability of making a Type I error is greater or equal to a significance level β. This probability is equal to 1-F (k N, n, r), where F (k) is the cumulative hypergeometric k | k distribution function of finding at least k positives in n samples drawn from a population of size N which contains r positives. This probability is also adjusted for multiple testing (Bonferroni-corrected). For further reference, we will refer to this as our β threshold. Fig. 3. The enriched model pathway of Aldehyde degradation. Base model pathway reactions are colored black; MaRIboES reactions are colored in red; and reactions that belong to both base model pathway and MaRIboES 3.3.2 Multi-step prediction We extended the work of de Groot reactions are colored in green. et al. [3] by automating multi-step predictions. A multi-step prediction is MaRIboES one-step prediction applied iteratively: the output of the previous prediction is used as the input compound of the next prediction. We formulated similar measures as in Section 3.3.1 to rank multi-step approaches in finding homologous sequences: BLAST and profile HMMs. predictions: combined posterior probability and significance test. Assuming Both approaches are complementary to each other in finding homologous independent predictions, the combined posterior probability of a multi-step enzymes. BLAST finds homologous sequences based on local alignments prediction (path) w is simply the multiplication of the individual posterior with every sequence in the training set. Hence, it is well-suited to find probability of every reaction in that path. sequences uniquely homologous to one of the sequence in the training set. Profile HMMs find homologous sequences based on multiple alignments of P (w) = P (i) several sequences. Therefore, they work well in detecting patterns that exist i w in multiple sequences: the drawback is that to build one profile HMM, one Y∈ needs at least two sequences (since it is built based on a sequence alignment). P (w) is the combined posterior probability of path w, Pi is the posterior Further discussion of both approaches can be found in the supplementary probability of the ith prediction in path w. If P (w) exceeds a threshold material. αm, we accept the prediction. As for the significance test, we set it up in a similar fashion as in the one-step prediction. We label a path ’positive’ if Each HMM profile and BLAST hit comes with an E-value that indicates every reaction found in that path is listed in BRENDA. If at least one reaction how significant the hit is. The smaller the E-value, the more significant the from that path is not found in BRENDA, the entire path will be labelled hit. We simply concatenate both HMM prediction and BLAST hits to arrive ’negative’. This is done for every set of paths that has the same enzymatic at a single result list. transformation patterns in the same order. Multi-step predictions for which the p-value calculated according to the hypergeometric distribution (exactly 3.5 Protein complex and isoenzyme detection as in section 3.3.1) exceeds a threshold βm are accepted. The problem one faces when trying to reconstruct metabolic networks is the detection of isoenzymes and protein complexes. Isoenzymes and proteins In enriching our model pathways, we simply add these reactions to the base in complexes receive the same EC number, although they may have very model pathways. If model pathways state that there are two reaction (EC different amino acid sequences. Using heterogeneous sequences to build one numbers) catalyzing compound A to compound B, and MaRIboES predicts HMM profile will decrease the effectiveness of a profile HMM model to another enzyme (different from the existing two) to catalyze the same detect a motif or important patterns among the sequences. As HMM profiles reaction, then the enriched model pathways will have three reactions (EC are built based on multiple sequence alignments, the models will be more numbers) going from compound A to compound B. In this proposed method, sensitive to detect homologous sequences similar to those it was trained we limit ourselves to three-step predictions due to computational complexity on. Using homogeneous sequences to build a profile HMM increases its involved. As an example, we provide the enriched model pathway of sensitivity to detect sequences with specific patterns (i.e. protein families). Aldehyde degradation (Figure 3). Therefore, we develop a mechanism to separate amino acid sequences into smaller, more homogeneous groups based on sequence similarity. 3.4 Finding homologs A reaction is said to exist in the reconstructed network if we can find Building the distance matrix enzyme(s) catalyzing it in the proteome of the organism being considered. For each reaction, we gather all amino acid sequences known to catalyze it. These enzymes are found via sequence homology. We employ two Let set A contain n such sequences (A = a1, a2, ..., an). We perform global

4 pairwise alignment on the set A. The result is an n n matrix S, in which × each element Sij is a similarity measure counting the number of amino acids matched over the entire alignment of ai and aj . Then, we convert the similarity measure into a dissimilarity score D as follows: D = 1 S . ij − ij Single-linkage clustering Based on the distance matrix, we perform single-linkage clustering on set A. The result is a dendogram reflecting how similar or dissimilar sequences in set A are. We find that there are n 1 ways to cut it. Each dendogram cut − corresponds to a way to group set A into 2,3,4, ... n clusters. We calculate the distances between successive dendogram cut points and denote it as set F (F = f1, f2, ..., f(n 2) ). The distance between these cut points describes { − } how distinctive the defined groups are. We sort the set F from maximum to minimum and use it as the order to cut the dendogram. For each cluster defined in each dendogram cut, we perform multiple sequence alignment. The result of each alignment is then used to build a profile HMM model. Therefore, we will have one profile HMM model for each cluster whose members are at least 2 sequences (the minimum number of sequences to produce an alignment). For each model, we compute the probability of each sequence in the proteome of the left-out organism to be emitted by it (i.e. the probability of the sequence given the model). Any hit whose E-value is lower than the optimum threshold (discussed in Section 3.6) is accepted (i.e. Fig. 4. Leave-one species-out cross-validation mechanism to find the the sequence is “recovered”). optimum number of clusters for building profile HMMs.

Leave-one species-out cross-validation To define the optimum number of groups within set A, we perform leave-one species-out cross-validation over all species that contribute sequence(s) to set Therefore, we are interested in finding the optimum combined parameter A. Let set O contains x organisms that contribute amino acid sequences to values rather than to find the optimum value for either individual parameter. set A, O = o1, o2, ..., ox . We build a distance matrix and perform single- We approached this problem by creating a modified version of ROC curve, { } linkage clustering x number of times, each time leaving out sequences from a rather than using the traditional one. To determine the optimum threshold single organism. The optimum number of clusters into which to divide the set for both parameters, we plot an ROC curve as we vary the threshold for A is the one that allows to recover most of the left out sequences. The overall both parameters. If we have n possible values for the first parameter and m optimal number of groups over all species is then selected via majority possible values for the second parameter, we will have nm points in our ROC voting. This mechanism is depicted in Figure 4. To reduce computation time, curve. Each point represents the false positive rate and true positive rate at we introduced several heuristics: if the number of organisms contributing a particular threshold for the first parameter and another particular threshold sequences to the training set exceeds 50, we perform 5-fold cross-validation for the second parameter. Then, we draw lines on the hull of these scattered rather than leave-one out and we stop iterating to the next dendogram cut points. In drawing the line, we take the optimal point (in terms of the true if the current dendogram cut performs worse (i.e. recovers less left-out positive rate) for every false positive rate. The line represents the point where sequences or recover the same number left-out sequences but with worse we cannot improve anymore in terms of true positive rate. Further details for E-values). each ROC curve we provide are as follows: 3.6 Experimental Setup In evaluating our performance, we used Saccharomyces cerevisiae as our test organism, reconstructed its metabolic network and assessed the Base model pathways reconstruction ROC curve (Figure 11), it performance by finding how many reactions can be correctly predicted. • measures the performance of our reconstructed metabolic networks We left out all its sequences and reactions unique to this organism in of Saccharomyces cerevisiae, which were based on the base model every component of the training phase (i.e. protein complex and isoenzyme pathways. detection, MaRIboES prediction, and base model pathway construction). Each prediction is labelled as either true positive (the reaction is predicted in the reconstructed network and is found in Saccharomyces cerevisiae), The MaRIboES ROC curve (Figure 5), it depicts the quality of false positive (the reaction is predicted in the reconstructed network, but • MaRIboES prediction as we vary the α and β thresholds. In plotting Saccharomyces cerevisiae false negative not found in ), (the reaction is this ROC curve, we left out reactions that occur only in Saccharomyces Saccharomyces cerevisiae in not the reconstructed pathway, but is in ), cerevisiae and retrained all MaRIboES classifiers. These classifiers are true negative and (the reaction is not predicted and does not exist in then used to predict enzymatic transformations on compounds that are Saccharomyces cerevisiae ). We summarize these measures in a receiver listed to be found in Saccharomyces cerevisiae. This resulted in 1577 operating characteristic (ROC) curve that plots the true positive rate against predictions that are plotted in this ROC curve. The color of each dot false positive rate. We define the true positive rate (TPR) and false positive represents the α threshold at a particular point. We also provided a rate (FPR) as: similar figure in the supplementary material, where each dot represents TP FP the β threshold at a particular point. TPR = ,FPR = TP + FN FP + TN In our case, we have two parameters to optimize for each ROC curve: the BLAST and HMM E-value thresholds for both the base model pathways Enriched model pathways reconstruction ROC curve (Figure 6), reconstruction ROC curve and the Enriched model pathways reconstruction • it reflects the quality of our reconstructed metabolic network of ROC curve and the α and β thresholds for the MaRIboES ROC curve. Saccharomyces cerevisiae using various enriched model pathways

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Source of true positives base 15% 20% 25% 28%

both MaRIboES & model pathway 0 12 17 20 32 MaRIboES only 0 28 40 51 53 total 296 324 336 347 349

number of pathways 76 76 76 76 76 Table 1. The statistics of true positive predictions based on the source of the true positives.

Fig. 5. ROC curves depicting the quality of maRIboES prediction as we vary while we vary them (Figure 5). Theoretically, we can define a set α β the two thresholds: the and thresholds. The dotted lines correspond to of enriched model pathways for every false positive rate found in threshold at 28%, 25%, 20%, and 15% false positive rate. The color of the Figure 5 and evaluate its impact on the overall performance of dots in the graph denotes the α threshold at a particular point. the reconstruction algorithm. Due to the computational complexity involved in carrying out such analysis, we limit ourselves to four sets of model pathways, enriched with MaRIboES predictions for which both thresholds are set to obtain 28%, 25%, 20%, and 15% false positive rate (FPR). The result is depicted in Figure 6, showing that the reconstructed networks based on the enriched model pathways have a higher false positive rate. However, they achieve higher true positive rate than the reconstructed pathway based on the base model pathways only. Table 1 takes a closer look at the source of these true positive predictions. The increase of true positive rate shown in Figure 6 is only attributed to the new true positives found by MaRIboES. As discussed in Section 3.6, if both model pathway and MaRIboES share a mutual prediction, it is only counted once for the calculation of our ROC curve. These new true positive predictions resulted from recovering left-out Saccharomyces cerevisiae-specific reaction, improving annotation, and finding possible isoenzymes. Each type of these true positives is discussed below:

Enriched model pathways recover left-out reactions of Saccharomyces cerevisiae Fig. 6. ROC curves depicting the performance of the reconstructed During the training process, we left out all reactions found only metabolic network based on base model pathways and model pathways in Saccharomyces cerevisiae. These reactions are therefore not enriched with MaRIboES predictions of 28%, 25%, 20%, and 15% false included in the model pathway. Hence, they will always result in positive rate false negatives, since we cannot even attempt to find the enzymes catalyzing them. Among the reactions added by MaRIboES, some of these left-out reactions can be found. For example, the versus base model pathways. If both MaRIboES and model pathways reaction from L-lactate to pyruvate. It is catalyzed by L-lactate share a prediction (both predict that there is a reaction from compound dehydrogenase, whose EC number is 1.1.2.3. MaRIboES predicted A to compound B), we only count it once. Therefore, any observed the same reaction with the correct EC number. Therefore, in the final increase in the true positive rate is exclusively caused by adding reconstructed pathway, we are able to find the homologous enzyme MaRIboES predictions. that catalyzes L-lactate to pyruvate (Figure 7). The full analysis A single measure for the quality of an ROC curve is the area under the curve on the statistics of these left-out reactions on the 76 reconstructed (AUC) which runs from 0.5 for random predictions to 1 for perfect ones. pathways of Saccharomyces cerevisiae is presented in Table 2. The fact that the number of left-out reactions recovered does not change as we vary the false positive rate used in the enrichment of our model 4 RESULTS AND DISCUSSIONS pathways indicates that these left out reactions are predicted with Enriched model pathways increase the true positive rate high confidence by MaRIboES. Hence, using the most stringent We compared the reconstruction result based on base model threshold (i.e. a 15% false positive rate), we are still able to recover pathways with that found using enriched model pathways. In them. enriching model pathways with MaRIboES reactions, we have two parameters that we can vary: the α and β thresholds. To determine Enriched model pathways improve annotation the optimum value for both parameters, we plot an ROC curve In curated databases, many reactions receive an incomplete EC

6 Fig. 11. An ROC curve that depicts the result of the reconstruction process based on base model pathways. The color of the dots reﬂects the log (BLAST − 10 E-value) threshold (left) and the log (HMM E-value) (right). − 10

base 15% 20% 25% 28%

number of left-out reactions 9 9 9 9 9 number of recoverred reactions 0 3 3 3 3 Table 2. The statistics of the number of recovered left-out reactions of Saccharomyces cerevisiae for each type of enriched model pathways.

Fig. 8. a) The reaction from N6-Acetyl-L-lysine to 2-keto-6- acetamidocaproate, as listed in SGD. This particular reaction receives an incomplete EC number of 2.6.1.-. b) The enriched model pathway improves the annotation of this reaction.

pathways, possible isoenzymes are the majority. Although we do not predict the same EC number as the one listed in the well-curated database, our reconstructed metabolic network is able to indicate that a reaction exists and suggests an enzyme that can catalyze it. As discussed in Section 3.6, the increase in true positives contributed by possible isoenzymes is due to the failure of finding homologous Fig. 7. a) The base model pathway excluding the reaction from L-lactate to enzyme(s) suggested by the base model pathways. One example pyruvate. b) The enriched model pathway recovers the left-out reaction. is the reaction from methylglyoxal to L-lactaldehyde . The model pathway assigns EC number 1.1.1.283 to it (Figure 9). MaRIboES added two alternative enzymes that can catalyze the same reaction number, MaRIboES can help by providing a complete one. (1.1.1.4 and 1.1.1.1). After the reconstruction process, we were not For example, in the lysine degradation pathway, the annotation able to find a homologous protein for EC number 1.1.1.283 and of the reaction N6-Acetyl-L-lysine + 2-oxoglutarate = 2-keto-6- 1.1.1.4; but we were able to find a homologous sequence for EC acetamidocaproate + L-glutamate is 2.6.1- (Figure 8a). MaRIboES number 1.1.1.1. Thus, we are able to predict an enzyme catalyzing predicted both the transformations from N6-Acetyl-L-lysine to 2- the reaction from methylglyoxal to L-lactaldehyde. keto-6-acetamidocaproate and 2-oxoglutarate to L-glutamate to be catalyzed by enzyme 2.6.1.42 (Figure 8b). The MaRIboES predicted Enriched model pathways suggest alternative pathways EC number matches the first three digits of the listed EC number in After performing MaRIboES’ one-step and multi-step predictions, SGD, suggesting this is the correct EC number for this reaction. the resulting enriched pathways are grown by 258 multi-step reactions (three steps). Most of these reactions extend the pathway; Enriched model pathways suggest possible isoenzymes a few of these suggest bypasses or alternative paths. For example, Among the new true positives we attain by using enriched model for the reaction between α-D-glucose 6-phosphate to α-D glucose

7 Melia et al

Fig. 12. The ROC compares the result of the HMM proﬁle with and without the clustering algorithm applied. 638 reactions are considered in the calculation of the ROC curve. The red dotted line corresponds to the HMM E-value threshold found in Section 4.1. Fig. 9. An example of an enriched model pathway suggesting possible isoenzymes. more trustworthy as it detects homology not based only a single sequence, but a set of sequences. For the rest of the discussion, we picked the operating point on this ROC curve (denoted by the red dotted line in Figure 11, left and right) as the threshold for our BLAST and HMM E-values. The motivation to pick such point is that the graph reached a plateau-like region after the operating point, where increasing the false positive rate does not add noticeable increase in the true positive rate.

Clustering helps to detect isoenzymes and protein complexes. We calculate the optimum number of clusters for every reaction considered in the reconstruction process, as discussed in Section 3.5. Fig. 10. An alternative two-step reaction is suggested by the enriched model For all 638 reactions, we compare the result of the HMM profile pathway, denoted by the red arrows. prediction with and without clustering algorithm applied (Figure 12). As the area under the curve (AUC) indicates, applying the clustering algorithm improves prediction results. Furthermore, at 1-phosphate, the base model pathway listed it to be catalyzed by the point of the operating point (indicated by the red dotted line, phosphoglucomutase (5.4.2.2). In the enriched model pathway, we calculated in Section 4.1), using clustering, we can achieve a higher found an alternative two-step reaction between the two compounds, true positive rate than originally. Another interesting observation is involving alpha-D-glucose (Figure 10). These two-step reactions the behavior of the algorithm performance after 28% false positive are not found in Saccharomyces cerevisiae nor in the model rate, where clustering actually impairs performance. This is caused pathways (other organisms). by the fact we cannot train HMM models for clusters that contains only a single sequence; leaving out unique sequences causes us to loose information in finding homologous proteins. This supports the 4.1 HMM E-value threshold has a larger influence than claim in Section 3.4 that the use of HMM profiles and BLAST are the BLAST E-value threshold complementary to each other in the reconstruction process. There are two parameters that we need to optimize, the HMM and BLAST E-value. These two parameters are calculated To highlight the advantage of applying the clustering algorithm, we independently of each other (Figure 11, left and right). The only provide two examples of when it helps discover isoenzymes and difference between the two figures is that in Figure 11 (left), the protein complexes, namely in the case of acetolactate synthase and color of each dot represents log (BLAST E-value); Whereas, in [Acyl-carrier protein] S-malonyltransferase. − 10 figure 11 (right), the color of each dot represents log (HMM E- − 10 value). Based on the pattern change of the coloring, we concluded In the Saccharomyces Genome Database [20], acetolactate synthase that the HMM E-value has a larger influence than the the BLAST E- is annotated with EC number 2.2.1.6 and composed of two subunits value on metabolic network reconstruction performance. This may that form a protein complex (Figure 13c). The catalytic subunit is be due to the nature of the HMM profile. which is built from a encoded by gene ILV2 and the regulatory subunit by gene ILV6. multiple sequence alignment that captures the similarity in a set of Without clustering, both BLAST and the HMM profile method can sequences, as opposed to BLAST that takes into account only the only find the catalytic subunit. After clustering, the HMM profile similarity with a single sequence. In a sense, the HMM E-value is method can find both subunits, with improved the E-values. The

8 Fig. 13. Protein complex.a) The result of the reconstruction process. We found two distinct proteins that catalyze the reaction from pyruvate to 2- aceto-lactate. BLAST only found one protein (UniProt accession number is P07342) and the HMM profile found two proteins (UniProt accession numbers P07342 and P25605). b) Single-linkage clustering on the 63 protein sequences annotated with EC number 2.2.1.6 (acetolactate synthase). After leave-one species-out cross-validation, the dendogram is cut at the optimum Fig. 14. Isoenzymes.a) The reaction from malonyl-CoA to malonyl- number of clusters (7). The HMM profile trained on the first cluster on the ACP is catalyzed by [Acyl-carrier-protein] S-malonyltransferase. The left found the protein sequence encoded by gene ILV2 and the HMM profile reconstruction lists that there are two enzymes catalyzing this reaction. One trained on the fourth cluster from the left found the protein sequence encoded enzyme is found by both BLAST and HMM (UniProt accession P07149) by gene ILV6. c) The gene-reaction schematic for acetolactate synthase and another enzyme is found only by HMM (UniProt accession number as listed in SGD ([20]). Further explanation on gene-reaction-schematic Q12283) b) Single-linkage clustering on the 29 amino acid sequences for is provided in the supplementary material. There are two reactions (two [Acyl-carrier-protein] S-malonyltransferase. After using leave-one species- boxes on the left) that this particular enzyme catalyzes; namely, pyruvate out cross-validation, we found that the optimum number of clusters is 2. + pyruvate + 2-oxobutanoate = 2-aceto-2-hydroxy-butyrate + CO2 and The HMM model trained on sequences from the leftmost cluster found pyruvate + pyruvate = 2-aceto-lactate + CO2. Both reactions are catalyzed the protein encoded by the gene FAS1 and the HMM model trained on by a protein complex whose subunits are proteins that are encoded by gene sequences from the second cluster from the left found the protein encoded ILV2 and ILV6. by gene MCT1. c) The gene-reaction schematic for [Acyl-carrier protein] S-malonyltransferase (2.3.1.39) as listed in SGD ([20]). There are two isoenzymes that can catalyze this reaction (the product of gene MCT1 and FAS1). The product of gene FAS1 is also denoted to catalyze four other protein encoded by gene ILV2 is found by the HMM model formed reactions. by the leftmost cluster (Figure 13b) and the protein encoded by gene ILV6 is found using the HMM model formed by the fourth cluster from the left. Note that the optimum number of clusters (7 clusters) found with our leave-one species-out cross-validation does the prediction. We improved this baseline method by developing a not always correspond with the number of clusters if we cut the clustering-based algorithm to detect isoenzymes/protein complexes dendogram at the largest “jump” (3 clusters). and by enriching our model pathways with reactions inferred based on functional homology. [Acyl-carrier protein] S-malonyltransferase is listed in SGD with EC number 2.3.1.39 (Figure 14c). There are two proteins that can Differences in implementation and input data prevent us from catalyze this reaction. They are fatty acid synthase (encoded by performing a meaningful comparison between our results with gene FAS1) and ACP transferase (encoded by gene MCT1). These those of Pireddu et al. [18]. However, our proposed addition of proteins do not form a protein complex in, but they are two different the clustering method and the enrichment using MaRIboES were enzymes able to catalyze the same reaction (isoenzyme). Before clearly shown to be useful. By applying our clustering algorithm, applying the clustering algorithm, both the BLAST and HMM we are able to homogenize our training set and divide them into profile methods are only able to find the fatty acid synthase. After smaller groups. Each group is more likely to allow detection applying the clustering algorithm and divide the training sequences of a certain homologous sequence than the whole. Enrichment into two clusters (the optimum number), both enzymes are found of MaRIboES-predicted reactions added another dimension to using HMM profile with improved E-values (Figures 14a and b). the existing sequence homology-based approaches. Functional homology information helps in the case where sequence-homology is undetected (i.e. failure to find homologous enzyme). We also assess the tradeoff between using base model pathway and enriched model pathways in terms of the completeness and the quality of the reconstructed metabolic networks. Finally, MaRIboES was shown 5 CONCLUSION to be useful in cases where we would like to achieve high sensitivity We have presented a method to automate metabolic network by sacrificing some enzyme specificity. reconstruction. It is based on Pireddu et al [18], using the union of all similar pathways across multiple organisms as a template for We also learned that combining the sequences from enzymes

9 Melia et al

listed by model pathways with sequences from enzymes inferred bibliomic data, PNAS, 104.6, 1777-1782. by MaRIboES produced no promising result (not shown). We [5]Eddy,S. (1998) Profile hidden markov models, Bioinformatics, 14, 755-763. postulate that validating MaRIboES-predicted reactions cannot be [6]Forster,J. (2003) Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network, Genome Res, 13, 244-253. done through sequences, as functional homology does not translate [7]Francke,C., Siezen,R., Teusink,B. (2005) Reconstructing the metabolic network of a into similarity in sequences. Hence, validating MaRIboES-predicted bacterium from its genome, Trends in Microbiology, 13, 550-557. reactions can only be performed through wet-lab experiments. [8]Gasteiger,E., Gattiker,A., Hoogland,C., Ivanyi,I., Appel,R., Bairoch,A., (2003) ExPASy: the proteomics server for in-depth protein knowledge and analysis, Nucleic Acids Res., 31, 3784-3788. Possible extension of our method is not only using the optimum [9]Green,M., Karp,P. (2004) A Bayesian method for identifying missing enzymes in number of clusters to determine the number of profile HMMs to predicted metabolic pathway databases, BMC Bioinformatics, 5, 76. build; but also in optimizing BLAST E-value threshold. Currently, [10]Hulo N., Bairoch A., Bulliard V., Cerutti L., Cuche B., De Castro E., Lachaize C., BLAST E-value threshold is determined based on the ROC curve Langendijk-Genevaux P.S., Sigrist C.J.A. (2008) The 20 years of PROSITE, Nucleic built from all predictions. This may not be the best approach, as a Acids Res., 36, D245-D249. [11]Kanehisa,M., Araki,M., Goto,S., Hattori,M., Hirakawa,M., Itoh,M., Katayama,T., family of orthologous proteins may not be as conserved as others. Kawashima,S., Okuda,S., Tokimatsu,T., Yamanishi,Y. (2008) KEGG for linking Therefore, the BLAST E-value threshold should be set accordingly genomes to life and the environment, Nucleic Acids Res., 36, D480-D484. (i.e. less stringent threshold for a family of orthologous proteins that [12]Karp,P., Paley,S., Romero,P. (2002) The pathway tools software, Bioinformatics, are less conserved). Choosing a different BLAST E-value threshold 18, S225-S232. [13]Karp,P., Riley,M., Pellegrini-Toole,A. (2002) The MetaCyc database, Nucleic Acids for each cluster in the training set may improve the overall true Res., 30, 59-61. positive rate and diminish the false positive rate. [14]Kharchenko,P., Vitkup,D., Church,G. (2004) Filling gaps in metabolic network using expression information, Bioinformatics, 20, i178-i185. We have accelerated proteome-wide metabolic networks reconstruction [15]Kolesov,G., Mewes,H., Frishman,D. (2001) SNAPping up functionally related from a partially-automated process into a fully-automated one. The genes based on context information: a colinearity-free approach, J. Mol. Biol., 311, 639-656. usability of our method is apparent as the data to build our prediction [16]Moriya,Y., Itoh,M., Okuda,S., Yoshizawa,AC., Kanehisa,M. (2007) KAAS: an tool is freely available from online databases in an enormous automatic genome annotation and pathway reconstruction server, Nucleic Acids Res., quantity. Unrestricted by the amount of data, our algorithm is 35, W182-5. applicable for current use. [17]Osterman,A., Overbeek,R. (2003) Missing genes in metabolic pathways: a comparative genomics approach, Current Opinion in Chemical Biology, 7, 238-251. [18]Pireddu,L., Szafron,D., Lu,P., Greiner,R. (2006) The Path-A metabolic pathway prediction web server, Nucleic Acids Res. 34, W714-719. REFERENCES [19]Rice,P., Longden,I., Bleasby,A. (2000) EMBOSS: The European molecular biology open software suite, Trends in Genetics, , 276-277. [1]Altschul,S., Gish,W., Miller,W., Myers,E., Lipman,D. (1990) Basic local alignment 16 [20]Saccharomyces Genome Database. (2009) , http://www.yeastgenome.org. search tool, J. Mol. Biol., 215, 403-410. [21]Thompson,J., Higgins,D., Gibson,T. (1994) Clustal W: improving the sensitivity [2]Barthelmes,J., Ebeling,C. (2007) BRENDA, AMENDA, and FRENDA: the enzyme of progressive multiple sequence alignment through sequence weighting, position- information system in 2007, Nucleic Acids Res., 35, D511-514. specific gap penalties, and weight matrix choice, Nucleic Acids Res., , 276-277. [3]de Groot,M., van Berlo,R., de Ridder,D. (2009) Metabolite and reaction inference 16 [22]Yamanishi,Y., Mihara,H., Osaki,M., Muramatsu,H., Esaki,N., Sato,T., Hizukuri,Y., based on enzyme specificities, Bioinformatics, 25(22), 2975-2982. Goto,S., Kanehisa,M. (2007) Prediction of missing enzyme genes in a bacterial [4]Duarte,N., Becker,S., Jamshidi,N., Thiele,I., Mo,M., Vo,T., Srivas,R., Palsson,B. metabolic network, FEBS Journal, , 2262-2273. (2007) Global reconstruction of the human metabolic network based on genomic and 274

10 Supplementary materials

0.1 Sequence similarity tools

BLAST BLAST starts by creating a word list from the query sequence (typically of length 3 for proteins). For example, if the query sequence is MYRPFL, there would be four words in the word list: MYR, YRP, RPF, and PFL. These words are used to scan the database for possible alignments. Any alignment whose score is at least T is called a hit. The algorithm requires two non-everlapping hits within distance A of one another on the same sequence to proceed. The next stage is that the second hit is extended in both directions until the running alignment’s score has dropped more than X below the current best score. This extension does not allow gaps. If the ungapped alignment’s score exceeds Sg, the gapped extension is triggered. The alignment is extended in both directions (allowing gaps) until the running alignment’s score has dropped more than Xg below the current best score. In this way, not all alignments trigger the gapped extension, which requires more calculation time.

Proﬁle HMM A Hidden Markov Model is a mathematical tool that can be used for sequence modelling. It captures characteristics of a set of input “training” sequences (a1, a2, ..., an) and uses it to make predictions about other sequence of the same alphabet (i.e. 20 amino acid letters). Hence, it can be used to evaluate whether an unseen sequence is of the same “kind” as (i.e. homologous to) sequences in the training data. An HMM model typically consists of a set of states an output alphabet, transition probabilities (i.e. probabilities to move between states), and emission probabilities (i.e. probability of emitting a certain alphabet in a certain state).

A profile HMM is a type of HMM architecture that is well-suited to represent profiles of multiple alignments. There are usually two alphabet-emitting-states, match and insert states; and there are three silent(i.e. non-emission) states to denote delete, start, and stop states. A profile HMM is built from an alignment of multiple sequences. For each column in the multiple alignment, there is a corresponding symbol-emitting state. An insert state can be used to insert one

1 or more symbols between one column and the next. The delete state may bypass one or more columns of the alignment. An example of a proﬁle HMM is depicted in Figure 1.

Suppose we have an alignment on which to train a proﬁle HMM(Figure 1(a)).

Figure 1: a) Alignment of three sequences, used to make a profile HMM b) Profile HMM that trained on the alignment in a). Mi denotes a match state at position i, Ii, denotes an insert state at position i, and Di denotes delete state at a certain position. The red path denotes the sequence of states that the first sequence takes. c) The null model.

The ﬁrst step is to determine the length of the HMM proﬁle (i.e., the number of match states). One heuristic to determine this is to only include columns that have amino acids in at least half of the sequences. In the above example, we would have 3 states: we leave out column 3 and 4. Next, we set emission probabilities. For each match and insert state, there is an emission probability for each alphabet/emitted symbol (i.e., 20 emission probabilities for the amino th acid alphabet). Let Pij is the probability of emitting amino acid i at the j position: N + p P = ij (1) ij N + 20(p) th Nij is the number of times amino acid i appears in j position, N is the number of aligned sequences, and p is a pseudocount (a small value added to every numerator and corrected in the denominator) to avoid zero probabilities. The transition probability going from state k to state l (Tkl) is :

tkl Tkl = (2) tk in which tkl is the number of times that the state k changes to state l and tk is the number of times that state k is visited. This probability can also be corrected by adding pseudocount to avoid zero probabilities. At this point, all transition probabilities and emission probabilities for the HMM proﬁle model have been set. The HMM proﬁle model can be used to calculate the probability of observing a sequence given an HMM model, P (sequence model). |

2 P (sequence model) = (P (sequence state sequence, model) P (state sequences model) | | × | X (3) This is a summation over all possible state sequences. To enumerate all possible state sequences, a dynamic programming approach is taken (the so-called “forward algorithm”).

Typically, one would like to know how well a sequence is explained by the model. The raw probability from the proﬁle HMM is turned into a score using the following formula:

P (sequence HMM model) Score = log | (4) P (sequence null model) | ! The null model (Figure 1c) is a simple HMM modelling a random sequence. It consists of one symbol emitting state whose emission probabilities typically are set to match amino acid residue composition of a large database (i.e. Uniprot). The null model has two transition probabilities: one to itself (typically set to be close to 1) and one to the end state.

A good proﬁle HMM model assigns high probability to sequences that are members of the same family as those in the training data, and low t other sequences. The rationale is that sequences from the same family have conserved regions at certain positions, where insertion and deletion does not typically happen. A proﬁle HMM is designed to capture this characteristic and detect it in a new sequence.

0.2 Gene-reaction-schematic

The gene-reaction schematic is a visual representation of the relationship among genes, enzymes, and reaction. The graph is read from left to right. Reactions are drawn in boxes and placed on the left side of the graph. Polypeptides/protein complexes are drawn in circles and are placed in the middle of the graph. On the right side of the graph, genes are drawn in boxes. Lines are drawn to connect these circles or boxes to denote relationship. A line from a reaction box to a circle encodes that the polypeptide/protein complex catalyzes such reaction. A line between circles encodes that those polypeptides form protein complexes. A line from a circle to a gene denotes that the polypeptide is the product of the gene.

3 Figure 2: The layout of the implementation details of our proposed approach.

0.3 Implementation Details

The implementation details of our proposed approach are discussed in six steps (as indicated in Figure 2). Input files are read by the parser and converted into meaningful biological objects (e.g. pathway, compound, sequence, etc). These objects are arranged inside their respective containers (i.e. hashtables) and are manipulated by other object classes (e.g. HierarchicalClustering, Distance- Matrix, and various wrapper classes). Among the generated output files are a pathway graph and a text file containing the statistics of all predictions made. The tool can be accessed via two files: optimizeParameter.cpp (training phase) and main.cpp (testing phase). Further discussion about each component is as follows:

1. Input files We have three input files that provide data for our prediction algorithm: MetaCyc files, UniProt files, and MaRIboES prediction result files. Beside these files, we also parse supporting input files (e.g. BRENDA). MetaCyc files contain the definition of pathways, reactions, compounds, and map- pings between its reactions with UniProt accession numbers (enzyme catalyzing each reaction). Protein sequences are provided by UniProt files. We divided these protein sequences into two groups based on the quality of annotation (manual or automated). We parse and arrange these proteins such that they can be accessed via accession number or its number. The third input files are MaRIboES prediction results. These files are parsed to gather statistics for each MaRIboES predictions (e.g. substrate, product, EC number, posterior probability, etc).

4 5

Figure 3: The class diagram for our proposed method. Arrows with non-solid heads denote inheritance relationships and lines with diamond heads denote aggregate relationships (i.e. one class is part of another). Relationship multiplicity is labelled where appropriate. Figure 4: a) Human representation of the three reactions between compound 2 and compound 4. b) Our internal representation of the same information on the left. A pathway is encoded as a 3-dimensional matrix. The direction of the reaction is embedded on its location (i.e. from the row to column). Red arrows denote pointers.

2. Parser Our parser is a collection of functions that read various input files and convert them into biologically meaningful objects (e.g. pathways, sequences, reactions, etc). The parser arranges these objects such that they can be easily retrieved for further data manipulation. The main reason that we compartmentalize various parsing functions together is to avoid having to redesign the entire implementation if we decide to change input files. 3. Collections of objects/classes The nature of our application is that we have a tremendous amount of data of different types (e.g. pathways, sequences, etc) that needs to be processed by various tools (e.g. BLAST, ClustalW, etc) iteratively. There- fore, we designed our implementation to ensure easy data retrieval and code reusability. Data and methods are handled by the various objects as defined in our class diagram (Figure 3). We grouped these classes into four groups, based on its functionality. They are: (a) Biological entities classes This is a collection of classes representing biologically meaningful information. These classes inherit from one parent class named BioN- ode. This design decision is taken because these classes share similar properties (i.e. they have ID, synonym, type, etc). This implies that all functions or data structures defined to operate on the parent class can automatically be used on its children classes. An example of how the various biological objects interact with each other (via C++ pointers) is depicted in Figure 4. (b) Container class One design issue that we faced in designing our implementation is

6 Figure 5: A pictorial presentation of the hashtable we use to store the various biological objects. Using this hashtable takes an expected O(1) time of insertion and deletion.

that we have to store a large amount of information (particularly sequences) whose access nature is random and frequent (as opposed to sequential access). Hence, we would like to avoid O(n) effort to fetch one information (e.g one sequence). The solution is to arrange our data in a hashtable in which insertion and deletion take O(1) time. Another characteristic of a hashtable is that if collision occurs (i.e. the hash function returns the same value given two different keys), we handle it by “chaining” (Figure 5). That is, we assign a pointer from the last element at that particular index to point to the new element. (c) Wrapper classes Wrapper classes encapsulate communication (e.g. sending requests and parsing results) to the various third-party tools we use in our approach. We developed one wrapper class for each third-party tool. Wrapper classes hide the details of each third-party tool from the rest of the objects. Hence, a change in the third-party tool will not affect the entire implementation. (d) Algorithm classes Due to the number of single-linkage clusterings we need to perform during the training phase (i.e. there are at least 638 reactions to an- alyze, at which one reaction may have sequences from three to hun- dreds of species), we store the distance between neighboring clusters using a sorted container (self-balancing binary search tree) whose complexity to find the minimum value is O(log n). Therefore, the total complexity for our hierarchical clustering is O(n2 log n) in- stead of the traditional single-linkage clustering that takes O(n3) to compute (scanning an n n matrix for n-1 times). × 4. Third-party tools We use BLAST to find local alignment, ClustalW2 to align multiple sequences, HMMER to make the profile HMM, EMBOSS to perform pairwise alignment, and GraphViz to draw graphs. 5. Output files

7 Output ﬁles that we produce are a reconstructed pathway (as a graph), statistics of our prediction, and the model pathway used for the prediction (drawn in graph). 6. Application’s front end The training phase can be accessed via

optimizeParameter.cpp

and the training phase via

main.cpp

0.4 Sequence diagrams

Sequence diagrams are used to explain the flow of data in a software. We provide three sequence diagrams: one for parsing, one for calculating the optimum cluster, and one for constructing metabolic networks. Although we leave out details, these sequence diagrams should reflect how we turn raw data (i.e. input files) into a reconstructed metabolic network.

8 9

Figure 6: Sequence diagram for parsing (part I) . 10

Figure 7: Sequence diagram for parsing (part II). 11

Figure 8: Sequence diagram for calculating the optimum number of clusters. 12

Figure 9: Sequence diagram for reconstructing metabolic networks (part I). 13

Figure 10: Sequence diagram for reconstructing metabolic networks (part II). Figure 11: ROC curve that depicts the quality of MaRIboES predictions as we vary the two threshold: the α and the β thresholds. The color of the dots depicts the normalized log(Probability of making a Type I error). − 0.5 Additional ﬁgure see Figure 11

14 Work Document

Tisha Melia

November 13, 2009 Contents

1 Document Update History 2

2 Automatic Reconstruction Tool 4

3 Parser 7 3.1 Internal representation of a graph ...... 8 3.2 Visualization ...... 8 3.3 Creating a Model Pathway ...... 8 3.4 Constructing Proﬁle HMM ...... 9 3.5 Calculating alignment score via BLAST ...... 11

4 Results 13 4.1 Automatic Gap Finding ...... 13 4.1.1 Integration with Mariboes ...... 14 4.1.2 TCA-Variants ...... 15 4.1.3 Parameter Optimization ...... 44 4.1.4 Finding the Optimum Number of HMM Models for each Reaction ...... 48 4.1.5 Contrasting the Performance of HMM models with and without Clustering ...... 52 4.1.6 Incorporating maRIboES Predictions into The Reconstruc- tion Process ...... 55

5 63 5.1 Determining MaRIboES cut-off ...... 63 5.2 Recovering organism-specific reactions ...... 63 5.2.1 Isoleucine Degradation ...... 64 5.2.2 Leucine Degradation ...... 64 5.2.3 Methylglyoxal Detoxification ...... 64 5.2.4 ROC Curve ...... 65

1 2 Chapter 1

Document Update History

Date Description 03-06-2009 Initial document creation 20-06-3009 Added section 1.4 (Types of Model Pathway), section 1.5 (Constructing HMM), section 1.6 (Support for Multithreading), and Chapter 2 (deliverables) 03-04-2009 Added Figure 2.2 (Automatic Reconstruction Tool), edited section 2.5 (Recon- structing HMM), added section 2.6 (Calculatingalignment via BLAST), and presented the result of HMM and blast (still in section 2.6). 16-04-2009 Added Figure 2.1 (Automatic Reconstruction Tool) and added three reconstructed pathways for Saccharomyces cerevisiae (pentose-phosphate, tca-cycle, and glycolysis) 27-04-2009 Updated data to metacyc13.0, automatized gap checking, Tested 22 pathways of Saccharomyces cerevisiae (found 30 gaps), and tested 3 pathways of Es- cherichia coli (found 21 gaps). 15-05-2009 Updated schematic overview of the system (Figure 2.2), updated the project timeline (appended at the end of the document), categorized gaps in Saccha- romyces cerevisiae into four types, provided flowchart of the automated gap checking and categorizing mechanism, and will give a presentation on what I have understood on mariboes from the paper and coding. 02-06-2009 Updated the four type of gaps, applied mariboes on the following pathways: tryptophan degradation, TCA-variants, and GLYCOLYSIS-variants, and compared the performance of the reconstruction tool before and after adding reactions inferred by mariboes. 15-06-2009 Added section 4.1.2 (guidelines in interpreting output graphs, statistics of TCA- variants reconstruction results, individual results for each compounds) and section 4.1.3 (planning/next step) 06-07-2009 Optimized BLAST e-value cutoff, optimized HMM e-value cutoff, and optimized mariboes posterior probability acceptance cutoff. 02-08-2009 Edited the Blast and HMM cutoff for section 4.1.3 (page 43-45) Added parameter optimization for maRIboES posterior probability cutoff and hypergeometric test cutoff in section 4.1.3 (page 46-47). Added section that explains about finding the optimum number of cluster for each set of training sequences (section 4.1.4). Added section that compares the performance of clustering the training sequences and not clustering the training sequences (section 4.1.5). Added section that explains the result of adding maRIboES inferred sequence into the reconstruction process (section 4.1.6). 31-08-2009 1)Added a new graph to3 determine maRIboES cut-offs (section 5.1). 2)Showed how maRIboES were able to predict Saccharomyces cerevisiae specific reactions in Leucine degradation, Isoleucine degradation, and Methylglyoxal Detoxifica- tion pathways (section 5.2). Chapter 2

Automatic Reconstruction Tool

Below is the high-level overview of the stystem (Figure 2.2). Another look at the schematic overview from software engineering point of view (Figure 2.2).

4 Figure 2.1: Step 1: This step takes in two inputs: list of pathways from multiple organisms (metacyc) and protein sequences from uniprot. Each pathway is represented as a graph that is stored in a two-dimensional matrix called an adjacency matrix. Each column and row of the adjacency matrix represent a compound. Each entry of the adjacency matrix may contain one or more reaction(s). The direction of the reaction is deﬁned from row to column. Step 2: This step takes all sequences that are attached to every enzyme that is found in the pathway and build an HMM model for each enzyme. These sequences will also be used as queries for the BLAST stand-alone server. Step 3: Recon- structing a metabolic pathway for a new organism. The input is the proteome of the new organism. The proteome is used by the BLAST stand-alone server as the database. Each sequence in the proteome is given to the HMM model to calculate the likelihood of the model emitting such sequence. Both BLAST and HMM model output a list of sequences (called hits) with their corresponding E-values. Any hit that is below 0.001 is used as n an evidence for a reaction to exist in the new organism. 5 Figure 2.2: The diagram depicts how each component of the system connect to each other. Arrows denote connection

6 Chapter 3

Parser

Figure 3.1 depicts how the parser handle Metacyc input files, create pathways, and visualize the pathways as graphs. There are three flatfiles that are treated as input files to create pathways. They are compound.dat, reaction.dat, and pathway.dat. Each of these input files are parsed and stored as objects (Figure 3.2). We defined three hashtables for each type of object (compound, reaction, and pathway). A Hashtable is created as an easy tool to find a certain object based on its name (uniqueId).

Figure 3.1: Each input files are stored into their respective hashtables. After setting up the hashtables, each pathway graph is created by creating an adjacency matrix. Each entry in the adjacency matrix contains reaction(s) that links compounds that is associated with a certain row and column. For a visualization aid, the adjacency matrix is traversed to create a dot file. A dot file is translated by GraphViz into a pdf file.

7 Figure 3.2: The class interaction diagram

3.1 Internal representation of a graph

A graph needs to be constructed for each object pathway. The graph is written in the form of an adjacency matrix. Each row and column of an adjacency matrix represents a certain compound in the pathway. An entry at a speciﬁc row and column denotes that there is a reaction going from the compound that is represented by the row to the compound that is represented by the column. Each entry in the adjacency matrix can contain several reactions (vector).

3.2 Visualization

For visualization, we created a graph for each pathway using GraphViz. GraphViz expects an input file that is written in the dot language to be parsed as a graph. The adjacency matrix is traversed (depth first search) to create an output that is written in the dot language. There is a dot file created for each pathway. Each dot file is translated into a pdf file by GraphViz. We have concatenated all pathways pdf files into the the file named pathways.pdf. Thus, pathways.pdf contains all the organism-specific pathways from metacyc.

3.3 Creating a Model Pathway

There are currently 1395 organism-speciﬁc pathways that are read from metacyc (see: pathways.pdf). Any of these pathways can be added to form a model pathway. In the context of our pathway object, creating a model pathway means computing the union of the adjacency matrices of the respective component pathways. As an example, we created a pathway model named GLYCOLYSIS- MODEL that is the union of the following pathways: GLYCOLYSIS I (page 154 in pathways.pdf), GLYCOLYSIS II (page 268 in pathways.pdf), GLYCOL- YSIS III (page 29 in pathways.pdf), GLYCOLYSIS IV, and GLYCOLYSIS V.

8 A simpliﬁed code snippet to create a model pathway is depicted as follows:

Pathway* P1 = hashtable.find(“GLYCOLYSIS I”); Pathway* P2 = hashtable.find(“GLYCOLYSIS II”); Pathway* P3 = hasthable.find(“GLYCOLYSIS III”); Pathway* P4 = hashtable.find(“GLYCOLYSIS IV”); Pathway* P5 = hashtable.find(“GLYCOLYSIS V”); ... vector componentPathway; //The component Pathway vector. ... P1, P2, P3, P4, and P4 is put inside the componentPathway vector .... Pathway* modelPathway = new Pathway(componentPathway) //the Pathway object is created as the union of P1, P2, P3, P4, and P5.

The result of the GLYCOLYSISMODEL can be found in page 5.

3.4 Constructing Proﬁle HMM

HMM model is used to model a Markov process with unobserved state changes. Typically, we observe symbol sequence (e.g., nucleotide, amino acid, etc), while the state sequence is hidden. The states of the HMM are often associated with meaningful biological labels, such as intron, exon, etc. In ﬁgure 3.3, the HMM model’s hidden states are 1 and 2. Whereas, the observed sequences are a and b.

Figure 3.3: An HMM model with two hidden states: 1 and 2. Each state can emit two symbols: a and b. ti,j denotes the transition from state i to j. Pi(a) denotes the probability of emitting symbol a in state i [1]

Proﬁle HMM is an HMM architecture that is well-suited to represent proﬁles of multiple alignments. There are usually two symbol-emitting-states: match, and insert states; and there are three silent states to denote delete, start and stop. For each column in the multiple alignment, there is a match state. An insert state can be used to insert one or more symbol between one column and

9 the next. The delete state may bypass one or more column of the alignment. An example of a proﬁle HMM is depicted in ﬁgure 3.4

Figure 3.4: An HMM proﬁle built from the ﬁve sequences on the left. b denotes as the begin/start state. e denotes as the end state. m1, m2, and m3 are the match states. i0, i1, i2, and i3 are the insert states. d1, d2, and d3 are delete states [1]

VGA--HAGEY V----NVDEV VEA--DVAGH VKG------D VYS--TYETS FNA--NIPKH IAGADNGAGY

Suppose we have the above alignments to build a profile HMM from: Determining the length of the HMM profile • One heuristic to determine the length of the HMM profile (i.e., the number of match states) is to only include columns that have amino acids in at least half of the sequences. In the above example, we would have 8 states. We leave out column 4 and 5. Setting emission probabilities For each match and insert states, there is an • emission probability for each alphabet/emitted symbol (i.e., 20 emission probabilities for amino acid). Pij is the probability of emitting amino acid i at the jth position: N P = ij (3.1) ij N th Nij is the number of times amino acid i appears in j position, N is the number of aligned sequences. We avoid zero probabilities by adding

10 a pseudo count for each emission probability. Thus the equation for Pij becomes: Nij +p N+20(p) Pij = (3.2) bi p is the pseudocount. To convert the probability to alignment score Sij = logPij

Setting transition probabilities Transition probability going from state k • to state l (Tkl) is : tkl Tkl = (3.3) tk

tkl is the number of times that the state k goes to state l and tk is the number of times that the state k goes to any state.

For every enzyme in the model pathway, we fetch its proteins sequences from Uniprot. Metacyc provides Uniprot accession numbers for each enzyme that exists in its database. Although, not all reactions in Metacyc is linked with an enzyme. These proteins are not only proteins that are found in the organism that made up the model pathway. These proteins are all proteins that are annotated with the same EC number of the reaction of interest. These proteins set are used to train the HMM.

We used HMMER, a freely distributable C/C++ based implementation of HMM to construct, train, and test our HMM model. There is one HMM model for each reaction per pathway. Steps to build the HMMs are described as follows:

1. Aligning proteins in the training set We have described how to gather protein sequences that made up the training set for each reaction in the above section. We aligned these proteins by using CLUSTALW2, a C/C++ implementation of multiple alignment tool. The input file for CLUSTALW2 is a fasta formatted file that contains proteins sequences that needs to be aligned. The output of this tool is called an aligned fasta file, which will be the input to train our HMM model. 2. Building HMM model To build and train an HMM model using HMMER, we pass the aligned fasta files to HMMER. The output is an hmm model.

3. Preparing the test set We constructed the test set by parsing the whole uniprot database. We grouped every protein based on the organism where it is found. The test set is located in /data/tera/tisha/output/test species. Each ﬁle is named after the species it is found. Thus, the ﬁle named Zy- momonasmobilis.fa contains all protein sequences that are found in Zy- momonas mobilis.

3.5 Calculating alignment score via BLAST

BLAST roughly works as follows:

11 1. Compile a list of high-scoring words create word list from the query sequence (typically of length 3 for • proteins). If the query sequence is MQAHLS, we would have 4 words in our word list: MQA, QAH, AHL, and HLS Scan the database for the above words. Any alignment whose score is • at least T is called a hit. The algorithm requires two non-everlapping hits that are found within distance A of one another on the same diagonal to proceed to the next stage.

2. Extending alignment of the second hit The second hit is extended in both direction (ungapped) until the running alignment’s score has dropped more than X below the current best score. A, X and T are parameters that can be set to tweak the sensitivity of BLAST search.

3. Gapped extension The gapped extension is only triggered if the alignment’s score exceeds Sg. The alignment is extended in both directions until the running alignment’s score has dropped more than Xg below the current best score. The resulting gapped alignment is reported only if it has a good enough score to be of interest. We installed a stand-alone BLAST server that reads input from uniprot flatfiles. Thus, the training and test sequences for HMM and BLAST are identical. The output of BLAST is in the form of XML file that is parsed by the program

12 Chapter 4

Results

4.1 Automatic Gap Finding

We formulated that there are three types of predictions and three types of gaps that may occur in a pathway.

Three types of predictions

Type of prediction Prediction is anno- Prediction is an- tated in a curated notated in a non- database curated database True Positive Yes N/A Possible Positive No Yes False Positive Type 2 No No Three types of gaps

Type of gap Training sequence Training sequence exists in curated exists in a non- database curated database False Negative Yes N/A Possible Negative No Yes True Negative No No Gaps are found in an automated fashion. The flowchart of the automated gap finding in Saccharomyces cerevisiae is depicted in figure 4.1.

13 Figure 4.1: Flowchart that depicts the automatic gap ﬁnding mechanism and the categorization of gaps

4.1.1 Integration with Mariboes In the previous section, we constructed pathways based only on model pathways, which are unions of pathways from multiple organisms. In this section, 14 we enrich model pathways with reactions that were inferred by Mariboes. Each compound in a model pathway is used as input to Mariboes. We included the inferred reaction(s) if the product of the reaction is found in the model pathway. We repeated the pathway reconstruction process again. But, we switched to the enriched model pathway as the template.

The output of our system is arranged in a pathway graph. Below is a guideline on how to interpret the graph: 1. Components of the graph Pathway graphs are made of compounds and reactions. A compound is represented by an elliptical node and a reaction is represented with a line with an arrowhead. To increase readability, there is only one line between every substrate-product pairs. If there are more than one reactions (isoenzymes) between the two compounds, it will be indicated on the label of the line. 2. Diﬀerent styles the line There are three diﬀerent styles of lines:

Black solid lines represent reaction from the original model path- • way. Black dotted lines represent reaction that were inferred by Mari- • boes. Enriched model pathways will contain both dotted and solid black lines. Red solid lines indicate that there is one or more reactions between • the two compounds which are gaps. 3. Rules of the labelling The label for each reaction contains the a unique Reaction ID that was assigned by Metacyc database and the status of the reaction (i.e., true positive, possible positive, false positive, hypothetical true positive, false negative, true negative, or possible negative).

4.1.2 TCA-Variants Overview of the result We applied the following steps to the TCA-variants pathway in yeast: 1. Set up the model pathway 2. Enrich model pathways with mariboes-inferred reactions (page 48) 3. Reconstructed pathway on yeast based on the original model pathway (page 49). 4. Reconstructed pathway on yeast based on the enriched model pathway (page 50(full) and page 51 (truncated)).We did not include all false positives in the truncated graph. We did the following to incorporate mariboes-inferred reactions into the model pathway:

15 1. Each mariboes-inferred reaction is added as a new reaction into the model pathway. Based on the EC number, we collected the training data and infer the results via HMM and Blast.

2. We added training sequences from mariboes-inferred reaction into the training sequences for known reaction. In other words, the training sequence of the known reaction contains both sequences listed in metacyc and inferred by mariboes.

We collected statistics to show the eﬀect of mariboes-inferred reactions to the reconstruction process. The results of the above steps are summarized in the following table: (TP stands for true positive, Hyp TP stands for hypothetical true positive, PP stands for possible positive, FP stands for false positive, TN stands for true negative, PN stands for possible negative, and FN stands for false negative). Hypothetical true positive is when the prediction’s EC number matches the mariboes EC number but not the actual EC number listed in metacyc.

Results of the two reconstruction processes: model pathway TP Hyp PP FP FN PN TN TP original 30 0 1 33 4 0 2 enriched 30 54 1 531 1 2 1

Details of the result There are 15 compounds in the TCA-VARIANTS pathway[refer to ﬁgure]. The discussion is divided per compound. For each compound, we only listed the reactions that consumes it. The full discussion is provided below:

1. acetyl-CoA In the original model pathway –model pathways that are not enriched with mariboes-inferred reactions–, acetyl-CoA is consumed in one reaction that produces citrate (ﬁgure 4.2). The reaction is annotated with the EC number of 2.3.3.1. Since none of the mariboes-inferred reaction produces citrate, we only use the reaction from the original model pathway for the reconstruction process. We made three predictions for the reaction from acetyl-CoA to citrate (ﬁgure 4.3). All predictions are annotated with the EC number of 2.3.3.1 in uniprot database. Thus, both predictions are labelled as true positives. All of the above information is summarized in the following tables:

List of Reactions for Acetyl-CoA in the enriched model pathways reaction ID product EC source CITSYN-RXN citrate 2.3.3.1 model pathway Results from the original reconstruction (based on model pathways)

16 Figure 4.2: Acetyl-CoA in the enriched model pathways. Enriched model pathways contain both reactions from the model pathway and mariboes. Solid lines denote reactions from the model pathway, while dotted lines denote mariboes- inferred reactions

Figure 4.3: Acetyl-CoA in the reconstructed pathway

reaction ID accession e-value prediction’s status EC CITSYN-RXN P00890 0 (blast) 2.3.3.1 true positive P08679 0 (blast) 2.3.3.1 true positive P43635 1.3e-118 2.3.3.1 true positive (blast) Results of the second reconstruction (based on enriched model pathways) reaction ID product EC accession status There is no added reaction from mariboes. Thus, the reconstruction result is no different than the one in the previous table 2. citrate In the enriched pathways, there is only one reaction that consumes citrate (figure 4.4). There is no new reaction added by mariboes. Thus, both results from the first reconstruct process (based on model pathways) and

17 the second reconstruction process (based on enriched model pathways) are identical (ﬁgure 4.5).

All of the above information is summarized in the following tables:

Figure 4.4: Citrate in the enriched model pathways. Enriched model pathways contain both reactions from the model pathway and mariboes. Solid lines denote reactions from the model pathway, while dotted lines denote mariboes-inferred reactions

Figure 4.5: Citrate in the reconstructed pathway

List of Reactions for citrate in the enriched model pathways reaction ID product EC source ACONITATEDEHYDR-RXN cis-aconitate 4.2.1.3 model pathway Results from the original reconstruction (based on model pathways)

18 reaction ID accession e-value prediction’s status EC ACONITATEDEHYDR-RXN P39533 0 (blast) 4.2.1.3 true positive P19414 0 (blast) 4.2.1.3 true positive P49367 1.20311e-30 4.2.1.36 false positive (blast) P07264 6.27555e-26 4.2.1.33 false positive (blast) P19414 0 (hmm) 4.2.1.3 true positive P39533 4.4e-217 4.2.1.3 true positive (hmm) Results of the second reconstruction (based on enriched model pathways) reaction ID product EC accession status There is no added reaction from mariboes. Thus, the reconstruction result is no diﬀerent than the one in the previous table 3. cis-aconitate There is only one reaction that uses cis-aconitate as a substrate in the model pathway. There is no reaction added by mariboes to the model pathway. Thus, the reconstruction process does not diﬀer between the one based on model pathway and the enriched pathway.

All of the above information is summarized in the following tables:

List of Reactions for cis-aconitate in the enriched model pathways reaction ID product EC source ACONITATEHYDR-RXN D-isocitrate 4.2.1.3 model pathway Results from the original reconstruction (based on model pathways) reaction ID accession e-value prediction’s status EC ACONITATEHYDR-RXN P39533 0 (blast) 4.2.1.3 true positive P19414 0 (blast) 4.2.1.3 true positive P49367 1.2e-30 4.2.1.36 false positive (blast) P07264 6.2e-26 4.2.1.33 false positive (blast) P19414 0 (hmm) 4.2.1.3 true positive P39533 4.4e-217 4.2.1.3 true positive (hmm) P07264 2.1e-05 4.2.1.33 false positive (hmm) P49367 9.4e-05 4.2.1.36 false positive (hmm) Results of the second reconstruction (based on enriched model pathways) reaction ID product EC accession status There is no added reaction from mariboes. Thus, the reconstruction result is no diﬀerent than the one in the previous table 4. D-isocitrate

19 There is three reactions that are linked with D-isocitrate. We also do not ﬁnd any added reaction from mariboes. Thus, the reconstruction process is not changed All of the above information is summarized in the following tables:

List of Reactions for D-isocitrate in the enriched model pathways reaction ID product EC source ISOCIT-CLEAV-RXN glyoxylate + succi- 4.1.3.1 model pathway nate ISOCITDEH-RXN 2-oxoglutarate 1.1.1.42 model pathway ISOCITRATE- 2-oxoglutarate 1.1.1.41 model pathway DEHYDROGENASE-NAD+- RXN Results from the original reconstruction (based on model pathways) reaction ID accession e-value prediction’s status EC ISOCIT-CLEAV-RXN P28240 0 (blast) 4.1.3.1 true positive B0KZR8 9.8e-141 2.3.3.9 false positive (blast) P30952 9.8e-141 2.3.3.9 false positive (blast) B0KZS7 1.3e-140 2.3.3.9 false positive (blast) B0L026 3.5e-140 2.3.3.9 false positive (blast) B0KZU5 4.9e-140 2.3.3.9 false positive (blast) B0KZY1 2.4e-139 2.3.3.9 false positive (blast) P21826 1.5e-132 2.3.3.9 false positive (blast) Q12031 3.6e-129 4.1.3.30 false positive (blast) Q4KQC3 2.5e-67 2.3.3.9 false positive (blast) Q4KQC4 2.7e-67 2.3.3.9 false positive (blast) Q4KQC8 6.9e-67 2.3.3.9 false positive (blast) Q4KQ91 9.0e-67 2.3.3.9 false positive (blast) Q4KQ64 5.9e-66 2.3.3.9 false positive (blast)

20 ISOCITDEH-RXN P21954 0 (blast) 1.1.1.42 true positive P41939 5.06975e-180 1.1.1.42 true positive (blast) P53982 4.68424e-165 1.1.1.42 true positive (blast) P28241 .86082e-76 1.1.1.41 false positive (blast) P28834 6.15583e-52 1.1.1.41 false positive (blast) P40495 9.10529e-46 1.1.1.87 false positive (blast) P04173 1.07725e-29 1.1.1.85 false positive (blast) P41939 1.2e-184 1.1.1.42 true positive (hmm) P21954 4.7e-184 1.1.1.42 true positive (hmm) P53982 4.1e-180 1.1.1.42 true positive (hmm) P28241 3.8e-67 1.1.1.41 false positive (hmm) P28834 2.8e-43 1.1.1.41 false positive (hmm) P40495 5.6e-42 1.1.1.87 false positive (hmm) P04173 4.1e-08 1.1.1.85 false positive (hmm) ISOCITRATE- P28241 1.36343e-173 1.1.1.41 true positive DEHYDROGENASE-NAD+- (blast) RXN P28834 3.41548e-169 1.1.1.41 true positive (blast) P40495 2.1325e-57 1.1.1.87 false positive (blast) P04173 1.80225e-33 1.1.1.85 false positive (blast) Q06350 3.08973e-11 3.2.1.14 false positive (blast) P21954 8.64961e-10 1.1.1.42 false positive (blast) P41939 4.82008e-07 1.1.1.42 false positive (blast) P53982 5.41733e-07 1.1.1.42 false positive (blast) P28241 4.4e-164 1.1.1.41 true positive (hmm) P28834 9.5e-159 1.1.1.41 true positive (hmm) P40495 1.6e-33 1.1.1.87 false positive (hmm) P04173 3.4e-12 1.1.1.85 false positive (hmm) 21 Results of the second reconstruction (based on enriched model pathways) reaction ID product EC accession status There is no added reaction from mariboes. Thus, the reconstruction result is no diﬀerent than the one in the previous table 5. glyoxylate There is only one reaction that consumes glyoxylate in the model pathay. We did not ﬁnd any reaction inferred by mariboes for glyoxylate. Therefore, the reconstruction process does not improve.

All of the above information is summarized in the following tables:

List of Reactions for glyoxylate in the enriched model pathways reaction ID product EC source MALSYN-RXN malate 2.3.3.9 model pathway Results from the original reconstruction (based on model pathways) reaction ID accession e-value prediction’s status EC MALSYN-RXN P21826 0 (blast) 2.3.3.9 true positive B0KZY1 0 (blast) 2.3.3.9 possible positive B0KZU5 0 (blast) 2.3.3.9 possible positive B0L026 0 (blast) 2.3.3.9 possible positive B0KZR8 0 (blast) 2.3.3.9 possible positive P30952 0 (blast) 2.3.3.9 true positive B0KZS7 0 (blast) 2.3.3.9 possible positive Q4KQC3 4.10553e-101 2.3.3.9 possible pos- (blast) itive Q4KQC4 1.44724e-100 2.3.3.9 possible pos- (blast) itive Q4KQC8 2.82118e-100 2.3.3.9 possible pos- (blast) itive Q4KQ91 3.87373e-100 2.3.3.9 possible pos- (blast) itive Q4KQ64 6.44611e-99 2.3.3.9 possible pos- (blast) itive P28240 1.43744e-37 4.1.3.1 false positive (blast) Q12031 1.0128e-36 4.1.3.30 false positive (blast) Results of the second reconstruction (based on enriched model pathways) reaction ID product EC accession status There is no added reaction from mariboes. Thus, the reconstruction result is no diﬀerent than the one in the previous table

22 6. succinyl-CoA succinyl-CoA are consumed by two reactions in the model pathway. We do not ﬁnd any inferred reaction by mariboes. Thus, the reconstruction process does not change. All of the above information is summarized in the following tables:

List of Reactions for succinyl-CoA in the enriched model pathways reaction ID product EC source SUCCCOASYN-RXN succinate 6.2.1.5 model pathway RXNI-2 succinate 2.8.3.5 model pathway Results from the original reconstruction (based on model pathways) reaction ID accession e-value prediction’s status EC SUCCCOASYN-RXN P53312 1.30651e-113 6.2.1.5 true positive (blast) P53598 3.64027e-74 6.2.1.5 true positive (blast) RXNI-2 none none none FALSE NEGATIVE Results of the second reconstruction (based on enriched model pathways) reaction ID product EC accession status There is no added reaction from mariboes. Thus, the reconstruction result is no diﬀerent than the one in the previous table 7. succinate semialdehyde In the model pathway, succinate semialdehyde is consumed by one reaction. We did not ﬁnd any reaction inferred by mariboes which involves succinate semialdehyde.

All of the above information is summarized in the following tables:

List of Reactions for succinate semialdehyde in the enriched model pathways reaction ID product EC source SUCCSEMIALDDEHYDROG- succinate 1.2.1.16 model pathway RXN Results from the original reconstruction (based on model pathways)

23 reaction ID accession e-value prediction’s status EC SUCCSEMIALDDEHYDROG- P38067 2.1398e-148 1.2.1.16 true positive RXN (blast) P40047 1.21204e-94 1.2.1.3 and false positive (blast) 1.2.1.4 P46367 4.32337e-82 1.2.1.3 false positive (blast) P47771 1.31226e-79 1.2.1.5 false positive (blast) P54114 1.84752e-79 1.2.1.5 false positive (blast) A9LRZ7 8.5132e-76 2.7.7.6 false positive (blast) P54115 8.5132e-76 1.2.1.3 false positive (blast) P32872 4.37225e-72 1.2.1.3 false positive (blast) P38694 6.57717e-45 1.2.1.- false positive (blast) P07275 2.31128e-26 1.5.1.12 false positive (blast) Q04458 7.4416e-22 1.2.1.- false positive (blast) P22281 5.79539e-21 1.2.1.3 false positive (blast) Results of the second reconstruction (based on enriched model pathways) reaction ID product EC accession status There is no added reaction from mariboes. Thus, the reconstruction result is no diﬀerent than the one in the previous table 8. 2-oxoglutarate Statistics collected on both reconstruction processes are summarized in the following tables:

List of Reactions for 2-oxoglutarate in the enriched model pathways reaction ID product EC source 2OXOGLUTARATEDEH-RXN succinyl-CoA not known model pathway 2-OXOGLUTARATE- succinyl-CoA 1.2.7.3 model pathway SYNTHASE-RXN MARIBOES-1.2.4.4-RXN succinyl-CoA 1.2.4.4 mariboes GLUTDEHYD-RXN L-glutamate 1.4.1.4 model pathway MARIBOES-2.6.1.42-RXN L-glutamate 2.6.1.42 mariboes RXN-7774 succinate semialde- 4.1.1.71 model pathway hyde

Results from the original reconstruction (based on model pathways)

24 reaction ID accession e-value prediction’s status EC 2OXOGLUTARATEDEH-RXN none none none true negative 2-OXOGLUTARATE- none 1.2.7.3 none false nega- SYNTHASE-RXN tive GLUTDEHYD-RXN P39708 0 1.4.1.4 true positive P07262 0 1.4.1.4 true positive RXN-7774 P20967 0 1.2.4.2 false positive Q45U08 0 2.2.1.2 false positive P19262 3.2e-17 2.3.1.61 false positive P12695 4.7e-14 2.3.1.12 false positive

Results of the second reconstruction (based on enriched model pathways) reaction ID product EC accession status 2OXOGLUTARATEDEH-RXN P32473 2.3e-65 1.2.4.1 false positive (blast) P16387 3.3e-33 1.2.4.1 false positive (blast) 2-OXOGLUTARATE- P32473 2.3e-65 1.2.4.1 false positive SYNTHASE-RXN (blast) P16387 3.3e-33 1.2.4.1 false positive (blast) MARIBOES-1.2.4.4-RXN P32473 2.3e-65 1.2.4.1 false positive (blast) P16387 3.3e-33 1.2.4.1 false positive (blast) GLUTDEHYD-RXN P39708 0 (blast) 1.4.1.4 true positive P07262 0 (blast) 1.4.1.4 true positive P47176 1.49e-110 2.6.1.42 hypothetical (blast) true positive P38891 2.4e-109 2.6.1.42 hypothetical (blast) true positive P53912 2.2e-32 3.-.-.- false positive (blast) P25608 5.3e-32 2.7.-.- false positive (blast) P54007 2.5e-31 1.-.-.- false positive (blast) P41696 3.1e-13 1.7.-.- false positive (blast) P47043 7.3e-11 2.7.10.2 false positive (blast)

25 P38753 9.0e-09 2.7.11.1 false positive (blast) P28625 1.4e-07 3.1.1.- false positive (blast) P43603 1.6e-07 2.7.1.67 false positive (blast) P00331 2.2e-07 1.1.1.1 false positive (blast) P32793 2.8e-07 3.6.3.14 false positive (blast) P53243 2.9e-07 3.1.26.4 false positive (blast) P53968 3.1e-07 3.4.21.42 false positive (blast) P38113 4.4e-07 1.1.1.1 false positive (blast) P39959 6.5e-07 3.1.1.- false positive (blast) P07248 2.0e-06 3.5.4.- false positive (blast) A2Q128 2.2-06 2.1.1.32 false positive (blast) P33748 2.3e-06 1.5.3.1 false positive (blast) P43601 3.4e-06 2.7.11.1 false positive (blast) MARIBOES-2.6.1.42-RXN P47176 1.49e-110 2.6.1.42 hypothetical (blast) true positive P38891 2.4e-109 2.6.1.42 hypothetical (blast) true positive P53912 2.2e-32 3.-.-.- false positive (blast) P25608 5.3e-32 2.7.-.- false positive (blast) P54007 2.5e-31 1.-.-.- false positive (blast) P41696 3.1e-13 1.7.-.- false positive (blast) P47043 7.3e-11 2.7.10.2 false positive (blast) P38753 9.0e-09 2.7.11.1 false positive (blast) P28625 1.4e-07 3.1.1.- false positive (blast) P43603 1.6e-07 2.7.1.67 false positive (blast) P00331 2.2e-07 1.1.1.1 false positive (blast) P32793 2.8e-07 3.6.3.14 false positive (blast)

26 P53243 2.9e-07 3.1.26.4 false positive (blast) P53968 3.1e-07 3.4.21.42 false positive (blast) P38113 4.4e-07 1.1.1.1 false positive (blast) P39959 6.5e-07 3.1.1.- false positive (blast) P07248 2.0e-06 3.5.4.- false positive (blast) A2Q128 2.2-06 2.1.1.32 false positive (blast) P33748 2.3e-06 1.5.3.1 false positive (blast) P43601 3.4e-06 2.7.11.1 false positive (blast) RXN-7774 P20967 0 1.2.4.2 false positive Q45U08 0 2.2.1.2 false positive P19262 3.2e-17 2.3.1.61 false positive P12695 4.7e-14 2.3.1.12 false positive 9. L-glutamate L-glutamate statistics on both reconstruction processes are summarized in the following tables:

List of Reactions for L-glutamate in the enriched model pathways reaction ID product EC source ASPAMINOTRANS-RXN 2-oxoglutarate + L- 2.6.1.1 model pathway aspartate MARIBOES-2.6.1.42-RXN 2-oxoglutarate 2.6.1.42 mariboes

Results from the original reconstruction (based on model pathways)

27 reaction ID accession e-value prediction’s status EC ASPAMINOTRANS-RXN P23542 1.11445e-106 2.6.1.1 true positive (blast) Q01802 1.34166e-73 2.6.1.1 true positive (blast) P47039 5.67659e-38 2.6.1.7 false positive (blast) P52893 3.28093e-29 2.6.1.2 false positive (blast) P52892 1.60183e-27 2.6.1.2 false positive (blast) Q66RF8 4.85915e-27 1.6.2.4 false positive (blast) P53090 7.90008e-13 2.6.1.57 false positive (blast) P07172 6.7376e-11 2.6.1.9 false positive (blast) P10356 6.68743e-08 2.1.1.- false positive (blast) P38840 4.81065e-07 2.6.1.57 false positive (blast) Q05567 1.96558e-05 4.1.2.27 false positive (blast)

Results of the second reconstruction (based on enriched model pathways)

28 reaction ID product EC accession status ASPAMINOTRANS-RXN P47176 1.49811e-110 2.6.1.42 hypothetical (blast) true positive P38891 2.41111e-109 2.6.1.42 hypothetical (blast) true positive P23542 1.11445e-106 2.6.1.1 true positive (blast) Q01802 1.34166e-73 2.6.1.1 true positive (blast) P47039 5.67659e-38 2.6.1.7 false positive (blast) P25608 5.3163e-32 2.7.-.- false positive (blast) P53912 2.23229e-32 3.-.-.- false positive (blast) P54007 2.57323e-31 1.-.-.- false positive (blast) P52893 3.28093e-29 2.6.1.2 false positive (blast) P52892 1.60183e-27 2.6.1.2 false positive (blast) Q66RF8 4.85915e-27 1.6.2.4 false positive (blast) P41696 3.14005e-13 1.7.-.- false positive (blast) P53090 7.90008e-13 2.6.1.57 false positive (blast) P07172 6.7376e-11 2.6.1.9 false positive (blast) P47043 7.34385e-11 2.7.10.2 false positive (blast) P38753 9.01989e-09 2.7.11.1 false positive (blast) P10356 6.68743e-08 2.1.1.- false positive (blast)

29 P28625 1.46924e-07 3.1.1.- false positive (blast) P43603 1.6027e-07 2.7.1.67 false positive (blast) P00331 2.28637e-07 1.1.1.1 false positive (blast) P32793 2.85025e-07 3.6.3.14 false positive (blast) P53243 2.92974e-07 3.1.26.4 false positive (blast) P53968 3.14552e-07 3.4.21.42 false positive (blast) P38113 4.45694e-07 1.1.1.1 false positive (blast) P38840 4.81065e-07 2.6.1.57 false positive (blast) P39959 6.555e-07 3.1.1.- false positive (blast) P07248 2.01738e-06 3.5.4.- false positive (blast) A2Q128 2.2915e-06 2.1.1.32 false positive (blast) P33748 2.3107e-06 1.5.3.1 false positive (blast) P43601 3.43544e-06 2.7.11.1 false positive (blast) P39010 4.51718e-06 2.3.1.- false positive (blast) P39943 4.69627e-06 2.7.11.1 false positive (blast) P53035 8.76294e-06 2.7.11.1 false positive (blast)

30 P33749 1.33263e-05 1.5.3.1 false positive (blast) P35183 1.85698e-05 3.4.24.21 false positive (blast) Q05567 1.96558e-05 4.1.2.27 false positive (blast) P00330 2.88975e-05 3.6.1.- false positive (blast) P39743 3.14593e-05 3.4.24.- false positive (blast) Q12013 0.00010495 2.3.1.- false positive (blast) P50086 0.000121957 4.1.1.65 false positive (blast) P27705 0.000134418 3.6.1.6 false positive (blast) P80667 0.000140082 2.3.1.- false positive (blast) P08153 0.000205252 3.6.1.- false positive (blast) Q66RF7 0.000212218 1.6.2.4 false positive (blast) Q12531 0.000212696 1.1.1.- false positive (blast) Q12041 0.000430422 2.7.7.4 false positive (blast) P07246 0.00049719 1.1.1.1 false positive (blast) Q12145 0.00057759 1.1.1.- false positive (blast) Q02486 0.000600803 3.2.1.55 false positive (blast) Q712M5 0.000600803 5.99.1.3 false positive (blast) Q00453 0.00062785 3.6.3.17 false positive (blast)

31 Q2VQD6 0.00069553 3.2.1.4 false positive (blast) P32805 0.000719135 3.6.5.- false positive (blast) P39933 0.000767226 2.3.1.48 false positive (blast) Q05937 0.000900843 3.1.3.69 false positive (blast) MARIBOES-2.6.1.42-RXN P47176 1.49811e-110 2.6.1.42 hypothetical (blast) true positive P38891 2.41111e-109 2.6.1.42 hypothetical (blast) true positive P53912 2.23229e-32 3.-.-.- false positive (blast) P25608 5.3163e-32 2.7.-.- false positive (blast) P54007 2.57323e-31 1.-.-.- false positive (blast) P41696 3.14005e-13 1.7.-.- false positive (blast) P47043 7.34385e-11 2.7.10.2 false positive (blast) P38753 9.01989e-09 2.7.11.1 false positive (blast) P28625 1.46924e-07 3.1.1.- false positive (blast) P43603 1.6027e-07 2.7.1.67 false positive (blast) P00331 2.28637e-07 1.1.1.1 false positive (blast) v P32793 2.85025e-07 3.6.3.14 false positive (blast) P53243 2.92974e-07 3.1.26.4 false positive (blast) P53968 3.14552e-07 3.4.21.42 false positive (blast) P38113 4.45694e-07 1.1.1.1 false positive (blast) P39959 6.555e-07 3.1.1.- false positive (blast) P07248 2.01738e-06 3.5.4.- false positive (blast) A2Q128 2.2915e-06 2.1.1.32 false positive (blast)

32 P33748 2.3107e-06 1.5.3.1 false positive (blast) P43601 3.43544e-06 2.7.11.1 false positive (blast) P39010 4.51718e-06 2.3.1.- false positive (blast) P39943 4.69627e-06 2.7.11.1 false positive (blast) P53035 8.76294e-06 2.7.11.1 false positive (blast) P33749 1.33263e-05 1.5.3.1 false positive (blast) P35183 1.85698e-05 3.4.24.21 false positive (blast) P00330 2.88975e-05 3.6.1.- false positive (blast) P39743 3.14593e-05 3.4.24.- false positive (blast) Q12013 0.00010495 2.3.1.- false positive (blast) P50086 0.000121957 4.1.1.65 false positive (blast) P27705 0.000134418 3.6.1.6 false positive (blast) P08153 0.000205252 3.6.1.- false positive (blast) Q66RF7 0.000212218 1.6.2.4 false positive (blast) Q12531 0.000212696 1.1.1.- false positive (blast) Q12041 0.000430422 2.7.7.4 false positive (blast) P07246 0.00049719 1.1.1.1 false positive (blast) Q12145 0.00057759 1.1.1.- false positive (blast) Q02486 0.000600803 3.2.1.55 false positive (blast) Q712M5 0.000600803 5.99.1.3 false positive (blast) Q00453 0.00062785 3.6.3.17 false positive (blast) Q2VQD6 0.00069553 3.2.1.4 false positive (blast) P32805 0.000719135 3.6.5.- false positive (blast) P39933 0.000767226 2.3.1.48 false positive (blast) Q05937 0.000900843 3.1.3.69 false positive (blast)

33 10. succinate The results of succinate reconstruction processes are summarized in the following tables:

List of Reactions for succinate in the enriched model pathways reaction ID product EC source SUCC-FUM-OXRED-RXN fumarate 1.3.99.1 model pathway SUCCINATE- fumarate 1.3.5.1 model pathway DEHYDROGENASE- UBIQUINONE-RXN R601-rxn fumarate 1.3.5.- model pathway SUCCCOASYN-RXN succinyl-CoA 6.2.1.5 model pathway MARIBOES-3.1.2.20-RXN succinyl-CoA 3.1.2.20 mariboes MARIBOES-6.2.1.1-RXN, 6.2.1.1 mariboes succinyl-CoA

Results from the original reconstruction (based on model pathways) reaction ID accession e-value prediction’s status EC SUCC-FUM-OXRED-RXN P47052 0 (blast) 1.3.5.1 false positive Q00711 0 (blast) 1.3.5.1 false positive P21801 3.7831e-87 1.3.5.1 false positive (blast) P32614 2.55073e-52 1.3.1.6 false positive (blast) P21375 5.40809e-50 1.11.1.15 false positive (blast) SUCCINATE- P47052 0 (blast) 1.3.5.1 true positive DEHYDROGENASE- UBIQUINONE-RXN Q00711 0 (blast) 1.3.5.1 true positive P21801 1.2894e-126 1.3.5.1 true positive (blast) P32614 1.21369e-22 1.3.1.6 false positive (blast) P21375 1.61782e-20 1.11.1.15 false positive (blast) P09624 0.00092531 1.8.1.4 false positive (blast) R601-RXN none none none true negative SUCCCOASYN-RXN P53312 1.30651e-113 6.2.1.5 true positive (blast) P53598 3.64027e-74 6.2.1.5 true positive (blast)

Results of the second reconstruction (based on enriched model pathways)

34 reaction ID product EC accession status SUCC-FUM-OXRED-RXN same as above SUCCINATE- same as above DEHYDROGENASE- UBIQUINONE-RXN R601-RXN same as above SUCCCOASYN-RXN Q01574 0 (blast) 6.2.1.1 hypothetical true positive P52910 0 (blast) 6.2.1.1 hypothetical true positive Q66RJ0 0 (blast) 1.6.2.4 false positive P53312 1.30651e-113 6.2.1.5 true positive (blast) P53598 3.64027e-74 6.2.1.5 true positive (blast) P38137 2.83246e-39 6.-.-.- false positive (blast) P07702 1.42493e-13 1.2.1.31 false positive (blast) P38225 5.56279e-09 6.-.-.- false positive (blast) P47912 1.59064e-05 6.2.1.3 false positive (blast) P30624 0.000198317 6.2.1.3 false positive (blast) MARIBOES-3.1.2.20-RXN none none none possible negative MARIBOES-6.2.1.1-RXN Q01574 0 (blast) 6.2.1.1 hypothetical true positive P52910 0 (blast) 6.2.1.1 hypothetical true positive Q66RJ0 0 (blast) 1.6.2.4 false positive P38137 2.83246e-39 6.-.-.- false positive (blast) P07702 1.42493e-13 1.2.1.31 P07702–false (blast) positive P38225 5.56279e-09 6.-.-.- P38225–false (blast) positive P47912 4.43896e-05 6.2.1.3 P47912–false (blast) positive P30624 8.20604e-05 6.2.1.3 P30624–false (blast) positive

11. fumarate Statistics collected from both reconstruction processes are summarized in the following tables:

List of Reactions for fumarate in the enriched model pathways reaction ID product EC source FUMHYDR-RXN malate 4.2.1.2 model pathway

35 Results from the original reconstruction (based on model pathways) reaction ID accession e-value prediction’s status EC FUMHYDR-RXN P08417 0 (blast) 4.2.1.2 true positive P04076 2.68641e-13 4.3.2.1 false positive (blast) Q05911 6.39355e-09 4.3.2.2 false positive (blast)

Results of the second reconstruction (based on enriched model pathways) reaction ID product EC accession status There is no added reaction from mariboes. Thus, the reconstruction result is no diﬀerent than the one in the previous table 12. phosphoenolpyruvate Results of the two reconstruction processes summarized in the following tables:

List of Reactions for phosphoenolpyruvate in the enriched model pathways reaction ID product EC source PEPCARBOX-RXN oxaloacetate 4.1.1.31 model pathway

Results from the original reconstruction (based on model pathways) reaction ID accession e-value prediction’s status EC PEPCARBOX-RXN none none none false negative

Results of the second reconstruction (based on enriched model pathways) reaction ID product EC accession status There is no added reaction from mariboes. Thus, the reconstruction result is no diﬀerent than the one in the previous table 13. malate Results of the reconstruction processes are summarized in the following tables:

List of Reactions for malate in the enriched model pathways

36 reaction ID product EC source MALATE-DEH-RXN oxaloacetate 1.1.1.37 model pathway RXNI-3 oxaloacetate 1.1.99.16 model pathway MALATE- oxaloacetate 1.1.99.16 model pathway DEHYDROGENASE- ACCEPTOR-RXN MARIBOES-1.1.1.1-RXN oxaloacetate 1.1.1.1 mariboes MARIBOES-1.1.1.2-RXN oxaloacetate 1.1.1.2 mariboes MARIBOES-1.1.1.276-RXN oxaloacetate 1.1.1.276 mariboes MARIBOES-1.1.1.280-RXN oxaloacetate 1.1.1.280 mariboes MARIBOES-1.1.1.4-RXN oxaloacetate 1.1.1.4 mariboes MARIBOES-1.1.2.3-RXN oxaloacetate 1.1.2.3 mariboes FUMHYDR-RXN fumarate 4.2.1.2 model pathway

Results from the original reconstruction (based on model pathways) reaction ID accession e-value prediction’s status EC MALATE-DEH-RXN Q6Q5N4 2.47512e-87 1.1.1.37 possible pos- (blast) itive P17505 4.30247e-85 1.1.1.37 true positive (blast) P32419 1.42548e-62 1.1.1.37 true positive (blast) P22133 2.01854e-58 1.1.1.37 true positive (blast) RXNI-3 none none none false negative MALATE- none none none false nega- DEHYDROGENASE- tive ACCEPTOR-RXN FUMHYDR-RXN P08417 0 (blast) 4.2.1.2 true positive P04076 2.68641e-13 4.3.2.1 false positive (blast) Q05911 6.39355e-09 4.3.2.2 false positive (blast)

Results of the second reconstruction (based on enriched model pathways)

37 reaction ID product EC accession status MALATE-DEH-RXN P38113 0 (blast) 1.1.1.1 hypothetical true positive P07246 1.19444e-169 1.1.1.1 hypothetical (blast) true positive P00331 2.2163e-166 1.1.1.1 hypothetical (blast) true positive P00175 5.46824e-166 1.1.2.3 hypothetical (blast) true positive P00330 3.09529e-165 1.1.1.1 hypothetical (blast) true positive P10127 3.11897e-131 1.1.1.1 hypothetical (blast) true positive P32771 1.62685e-123 1.1.1.284 hypothetical (blast) true positive Q6Q5N4 2.47512e-87 1.1.1.37 possible pos- (blast) itive P17505 4.30247e-85 1.1.1.37 true positive (blast) Q04018 2.98645e-81 3.4.-.- false positive (blast) P38715 5.93767e-64 1.1.1.- false positive (blast) P32419 1.42548e-62 1.1.1.37 true positive (blast) Q12458 2.97168e-62 1.1.1.- false positive (blast) P14065 3.63052e-62 1.1.1.- false positive (blast) P22133 2.01854e-58 1.1.1.37 true positive (blast) Q04894 1.11748e-49 1.1.1.2 hypothetical (blast) true positive Q05016 3.04203e-45 1.-.-.- false positive (blast) P38115 8.90921e-45 1.1.1.117 false positive (blast)

38 P25377 3.72113e-44 1.1.1.2 hypothetical (blast) true positive P25337 6.42778e-41 2.7.11.1 false positive (blast) P47137 5.88018e-40 1.-.-.- false positive (blast) P38182 6.70131e-36 2.4.2.- false positive (blast) Q07786 2.38446e-33 1.1.1.14 false positive (blast) P35497 1.01837e-32 1.1.1.14 false positive (blast) Q07551 4.78556e-31 1.2.1.- false positive (blast) Q03048 9.07001e-30 3.6.1.- false positive (blast) Q07993 2.53301e-26 1.1.1.9 false positive (blast) Q6Q5N8 2.05067e-25 2.2.1.2 false positive (blast) P46955 2.08517e-25 3.5.1.23 false positive (blast) P36135 1.18266e-24 2.7.1.23 false positive (blast) Q12068 2.02839e-24 1.1.1.283 false positive (blast) P53111 3.9212e-24 1.1.1.- false positive (blast) Q03049 7.70786e-24 1.1.1.- false positive (blast) P38230 8.55894e-24 1.6.5.5 false positive (blast) P40472 1.00147e-22 6.3.2.- false positive (blast) P53183 1.83619e-22 1.1.1.- false positive (blast) P53616 3.41441e-22 1.5.1.3 false positive (blast) P39714 3.81791e-21 1.1.1.4 hypothetical (blast) true positive Q6B208 4.11565e-21 1.5.1.3 false positive (blast) P04821 1.97019e-18 2.7.11.22 false positive (blast) P14771 2.34818e-17 3.6.1.- false positive (blast) P39713 1.03791e-16 1.-.-.- false positive (blast) P40579 4.14494e-14 1.-.-.- false positive (blast) P40580 1.00375e-13 1.-.-.- false positive (blast) 39 Q54AB5 1.00375e-13 1.-.-.- false positive (blast) P40471 8.78561e-13 1.1.1.101 false positive (blast) Q45U07 1.19632e-12 2.2.1.2 false positive (blast) P38286 6.6175e-12 1.1.1.- false positive (blast) Q07540 1.21174e-11 1.3.99.1 false positive (blast) Q04779 2.16563e-11 2.7.13.3 false positive (blast) P47156 3.3361e-10 1.14.11.- false positive (blast) Q12184 5.22182e-10 1.14.19.- false positive (blast) P25300 8.86691e-10 1.1.1.5 false positive (blast) P40312 1.75058e-08 4.4.1.8 false positive (blast) Q07530 3.87656e-08 1.-.-.- false positive (blast) Q03529 4.68569e-08 1.-.-.- false positive (blast) Q04772 3.77298e-07 2.7.11.1 false positive (blast) P38342 5.2464e-07 1.1.1.102 false positive (blast) P35731 2.79899e-06 1.-.-.- false positive (blast) Q08651 2.83033e-06 1.1.1.- false positive (blast) Q02207 3.45784e-06 1.1.1.- false positive (blast) P22217 4.96576e-06 1.8.1.9 false positive (blast) Q12177 1.31066e-05 3.2.1.- false positive (blast) P53250 2.0473e-05 3.1.3.48 false positive (blast) P07866 2.97649e-05 2.7.10.1 false positive (blast) P25372 4.06579e-05 1.8.1.9 false positive (blast) P32573 0.000137035 1.3.1.34 false positive (blast) P36086 0.000326356 3.1.2.- false positive (blast) Q04991 0.000470578 1.-.-.- false positive (blast) P54007 0.000551037 1.-.-.- false positive (blast) P38697 0.00076449 1.1.1.205 false positive (blast)

40 RXNI-3 P38113 0 (blast) 1.1.1.1 hypothetical true positive P07246 1.19444e-169 1.1.1.1 hypothetical (blast) true positive P00331 2.2163e-166 1.1.1.1 hypothetical (blast) true positive P00175 5.46824e-166 1.1.2.3 hypothetical (blast) true positive P00330 3.09529e-165 1.1.1.1 hypothetical (blast) true positive P10127 3.11897e-131 1.1.1.1 hypothetical (blast) true positive P32771 1.62685e-123 1.1.1.284 hypothetical (blast) true positive Q04018 2.98645e-81 3.4.-.- false positive (blast) P38715 5.93767e-64 1.1.1.- false positive (blast) Q12458 2.97168e-62 1.1.1.- false positive (blast) P14065 3.63052e-62 1.1.1.- false positive (blast) Q04894 1.11748e-49 1.1.1.2 hypothetical (blast) true positive Q05016 3.04203e-45 1.-.-.- false positive (blast) P38115 8.90921e-45 1.1.1.117 false positive (blast) P25377 3.72113e-44 1.1.1.2 hypothetical (blast) true positive P25337 6.42778e-41 2.7.11.1 false positive (blast) P47137 5.88018e-40 1.-.-.- false positive (blast) Q07786 2.38446e-33 1.1.1.14 false positive (blast) P35497 1.01837e-32 1.1.1.14 false positive (blast) Q07551 4.78556e-31 1.2.1.- false positive (blast) Q03048 9.07001e-30 3.6.1.- false positive (blast) Q07993 2.53301e-26 1.1.1.9 false positive (blast)

41 Q6Q5N8 2.05067e-25 2.2.1.2 false positive (blast) P46955 2.08517e-25 3.5.1.23 false positive (blast) P36135 1.18266e-24 2.7.1.23 false positive (blast) Q12068 2.02839e-24 1.1.1.283 false positive (blast) P53111 3.9212e-24 1.1.1.- false positive (blast) Q03049 7.70786e-24 1.1.1.- false positive (blast) P38230 8.55894e-24 1.6.5.5 false positive (blast) P40472 1.00147e-22 6.3.2.- false positive (blast) P53183 1.83619e-22 1.1.1.- false positive (blast) P53616 3.41441e-22 1.5.1.3 false positive (blast) P39714 3.81791e-21 1.1.1.4 hypothetical (blast) true positive 46 other false positives MALATE- same as RXNI-3 DEHYDROGENASE- ACCEPTOR-RXN MARIBOES-1.1.1.1-RXN P38113 0 (blast) 1.1.1.1 hypothetical true positive P07246 1.19444e-169 1.1.1.1 hypothetical (blast) true positive P00331 2.2163e-166 1.1.1.1 hypothetical (blast) true positive P00330 3.09529e-165 1.1.1.1 hypothetical (blast) true positive P10127 3.11897e-131 1.1.1.1 hypothetical (blast) true positive P32771 1.62685e-123 1.1.1.1 hypothetical (blast) true positive Q04018 2.98645e-81 3.4.-.- false positive (blast) P38182 6.70131e-36 2.4.2.- false positive (blast) P25377 1.89267e-35 1.1.1.2 false positive (blast) Q04894 2.53456e-35 1.1.1.2 false positive (blast) Q07786 2.38446e-33 1.1.1.14 false positive (blast) 25 other false positives

42 MARIBOES-1.1.1.2-RXN P32771 3.01743e-85 1.1.1.284 false positive (blast) P38715 5.93767e-64 1.1.1.21 false positive (blast) Q12458 2.97168e-62 1.1.1.- false positive (blast) P14065 3.63052e-62 1.1.1.- false positive (blast) Q04894 1.11748e-49 1.1.1.2 hypothetical (blast) true positive P38115 8.90921e-45 1.1.1.117 false positive (blast) P25377 3.72113e-44 1.1.1.2 hypothetical (blast) true positive P47137 5.88018e-40 1.-.-.- false positive (blast) P00331 6.75054e-33 1.1.1.1 false positive (blast) P00330 2.34092e-31 1.1.1.1 false positive (blast) P38113 2.90805e-31 1.1.1.1 false positive (blast) Q07551 4.78556e-31 1.2.1.- false positive (blast) 16 other false positives MARIBOES-1.1.1.276-RXN Q05016 3.04203e-45 1.-.-.- false positive (blast) P40579 4.14494e-14 1.-.-.- false positive (blast) P40580 1.00375e-13 1.-.-.- false positive (blast) Q54AB5 1.00375e-13 1.-.-.- false positive (blast) P40471 8.78561e-13 1.1.1.101 false positive (blast) Q45U07 1.19632e-12 2.2.1.2 false positive (blast) P38286 6.6175e-12 1.1.1.- false positive (blast) P38342 5.2464e-07 1.1.1.102 false positive (blast) Q08651 2.83033e-06 1.1.1.- false positive (blast) Q02207 3.45784e-06 false positive (blast) P32573 0.000137035 1.3.1.34 false positive (blast) MARIBOES-1.1.1.280-RXN none none none possible negative

43 MARIBOES-1.1.1.4-RXN P25337 6.42778e-41 25337–false (blast) positive P22217 4.96576e-06 22217–false (blast) positive MARIBOES-1.1.2.3-RXN P00175 5.46824e-166 1.1.2.3 hypothetical (blast) true positive Q07540 1.21174e-11 1.3.99.1 false positive (blast) P40312 1.75058e-08 4.4.1.8 false positive (blast) Q03529 4.68569e-08 1.-.-.- false positive (blast) Q04772 3.77298e-07 2.7.11.1 false positive (blast) Q04991 0.000470578 1.-.-.- false positive (blast) P38697 0.00076449 1.1.1.205 false positive (blast) FUMHYDR-RXN same as above (original reconstruction)

14. oxaloacetate Results of the two reconstruction processes are summarized in the following tables:

List of Reactions for oxaloacetate in the enriched model pathways reaction ID product EC source ASPAMINOTRANS-RXN 2-oxoglutarate + L- 2.6.1.1 model pathway aspartate CITSYN-RXN citrate 2.3.3.1 model pathway MALATE-DEH-RXN malate 1.1.1.37 model pathway All three reactions above have been discussed in previous compounds. The results are identical. Thus, we refer the reader to previous tables. 15. L-aspartate Statistics on the L-aspartate reconstruction processes are summarized in the following tables:

List of Reactions for L-aspartate in the enriched model pathways reaction ID product EC source No reaction is found which consumes L-aspartate

4.1.3 Parameter Optimization Parameter optimization analysis is provided in the form of ROC curves, where the false positive rate is plotted against the true positive rate. We deﬁned the false positive rate (FPR) as:

FP FPR = (4.1) FP + TN

44 and the true positive rate (TPR) as:

TP TPR = (4.2) TP + FN

Blast E-value cutoff We provided two ROC curves to show the optimal BLAST E-value cutoff. One ROC curve is to show the dynamics of FPR and TPR in terms of the number of prediction (figure 4.6). Whereas, the other ROC curve showed the number FPR and TPR in terms of reaction (figure 4.7).

Figure 4.6: ROC curve (prediction-wise) by changing the BLAST e-value cutoﬀ

The ROC curve for prediction shows that the value 5.1576e-127 is the optimum value for the BLAST e-value cutoﬀ.

45 Figure 4.7: ROC curve (reaction-wise) by changing the BLAST e-value cutoﬀ

HMM E-value cutoff We provided two ROC curves to show the optimal HMM E-value cutoff. One ROC curve is to show the dynamics of FPR and TPR in terms of the number of prediction (figure 4.8). Whereas, the other ROC curve showed the number FPR and TPR in terms of reaction (figure 4.9).

Figure 4.8: ROC curve (prediction-wise) by changing the HMM e-value cutoﬀ

Both of ROC curves shows that the value 9 e-123 is the optimum value for the BLAST e-value cutoﬀ.

46 Figure 4.9: ROC curve (reaction-wise) by changing the HMM e-value cutoff maRIboES Posterior Probability Acceptance cutoff for One-Step Pre- diction To find the optimal maRIboES posterior probability acceptance cutoff, we excluded all reactions (and compounds) that only belong to Saccharomyces cerevisiae and retrained all classifiers. The original 89 classifiers of maRIboES is reduced to 66 classifiers. We gathered all one-step predictions on TCA- VARIANTS pathway. We only considered predictions whose both substrates and products are found in the TCA-VARIANTS pathway. This restriction only, has filtered out most of maRiboES predictions. We produced an ROC curve based on the false positive rate and the true positive rate which were previ- ously defined. A prediction is denoted as a true positive if the transformation produces the correct product and uses the correct EC number as listed for Sac- charomyces cerevisiae in BRENDA. We gathered 98 compounds that are found in Saccharomyces cerevisiae and used the 66 classifiers to predict possible transformations. These predictions are collected to build the the following ROC curve (Figure 4.10).

The figure 4.10 suggests that 30 percent of false positive rate corresponds to setting the posterior probability cutoff at 0.008. The number may seem very low. But, this ROC curve was reconstructed using only a subset of all predictions. We only included predictions whose products are found in the TCA-VARIANTS pathway. In a sense, this is an added filtering to the predictions. maRIboES Hypergeometric Test Cutoff for One-Step Prediction We used the same set of predictions we used to determine the posterior probability: the set of predictions that only involves substrates and products that are found in the TCA-VARIANTS pathway. The cutoff is also found via an ROC curve which is depicted below (Figure 4.11 )

47 Figure 4.10: ROC curve to ﬁnd the optimum cutoﬀ for the posterior probability of maRIboES one-step prediction.

Figure 4.11: ROC curve to find the optimum cutoff for the hypergeometric test for maRIboES one-step prediction. The cutoff is depicted in terms of its -log10

We chose to accept 30 percent false positive rate, it corresponds to setting the cutoﬀ at 0.0840.

4.1.4 Finding the Optimum Number of HMM Models for each Reaction It is observed that the HMM models are not as sensitive predictors as BLAST. We assumed that this is caused by putting divergent sequences to make the HMM models. We hypothesized that if we divide the training set into one or more groups of related sequences and use each group to make its own HMM

48 model, we will improve the the sensitivity of the HMM models. To ﬁnd the optimum number of group (cluster) for each reaction, we do the following: 1. Building a distance matrix Since we are are trying to reconstruct Saccharomyces cerevisiae pathways, we excluded all sequences and reactions that only belongs to Sac- charomyces cerevisiae. For each reaction in the model pathway, there is a set of training sequences. We do pairwise alignment for each possible sequence pairs. Thus, we would have N N matrix of alignment scores for a training set of N sequences. To calculate× the distance matrix, for each sequence pair, we compute:

Scorei,j Di,j = 1 (4.3) − Li,j

Di,j is the distance between sequence i and sequence j, Scorei,j is the number of matched bases according to BLOSUM62 matrix, and Li,j is the length of alignment of sequence i and j. 2. Clustering the sequences based on the distance matrix (Figure 4.12 (right)) We opted to use single-linkage clustering. We also tried average and complete linkage clustering. Based on visual inspection of the dendograms. single linkage shows more distinct groups than other types of linkage.

Figure 4.12: (left)An example of clustered training sequences which leads to three distinct groups. (right) The fusion graph for the dendogram on the left

3. Finding the optimum number of clusters for each reaction For each dendogram, we computed a fusion graph (Figure 4.12) showing the jumps between the cluster size. We sorted the possible places to cut the dendogram (cluster size) based on the distance between the clusters/ jumps in the fusion graph. To ﬁnd the optimum cutoﬀ for each reaction, we do leave-one-out cross validation in terms of species and iterate the following procedure: Remove all sequences from a certain species from the training set. • Cluster the remaining sequences. •

49 Cut the dendogram at the largest jump in the fusion graph. • Make an HMM model for each cluster that is made up by more than • one sequence. Test the HMM model on the proteome of the left-out species. • Keep track of the number of true positives and the maximum E- • value of the true positive prediction. Continue to the next iteration of cutting the next largest jump in the fusion graph. Iteration stops if the number of true positive drops; or the number of true positive stays the same, but the E-value attained increases. Continue the same procedure for the next species in the training set. • The optimum number of clusters is chosen via the majority voting • after the cross validation iterations are done. If there is a tie, the smaller number of cluster is chosen.

If the reaction contains more than 50 species, we do 5-fold cross validation to save computation time. In the case of a training set that only has one species, we choose to cut the dendogram at the highest jump in the fusion graph. Below is the table listing the optimum cluster size for each reaction in the TCA- VARIANTS pathway.

50 reaction ID product substrate Optimum cluster size MALATE-DEH-RXN malate oxaloacetate 9 RXNI-3 malate oxaloacetate 2 MALATE- malate oxaloacetate 2 DEHYDROGENASE- ACCEPTOR-RXN FUMHYDR-RXN malate fumarate 5 CITSYN-RXN acetyl-CoA citrate 3 + oxaloacetate ASPAMINOTRANS-RXN L-aspartate L-glutamate 27 + 2- + oxaloac- oxoglutarate etate ACONITATEDEHYDR-RXN citrate cis-aconitate 3 ACONITATEHYDR-RXN cis-aconitate D-isocitrate 3 ISOCIT-CLEAV-RXN D-isocitrate glyoxylate + 3 succinate ISOCITDEH-RXN D-isocitrate 2- 6 oxoglutarate ISOCITRATE- D-isocitrate 2- 6 DEHYDROGENASE-NAD+- oxoglutarate RXN SUCC-FUM-OXRED-RXN succinate fumarate 3 SUCCINATE- succinate fumarate 2 DEHYDROGENASE- UBIQUINONE-RXN SUCCCOASYN-RXN succinyl- succinate 3 CoA MALSYN-RXN glyoxylate malate 3 RXN-7774 2- succinate 6 oxoglutarate semialdehyde 2-OXOGLUTARATE- 2- succinyl- 3 SYNTHASE-RXN oxoglutarate CoA GLUTDEHYD-RXN 2- L-glutamate 2 oxoglutarate SUCCSEMIALDDEHYDROG- succinate succinate only 1 se- RXN semialde- quence hyde RXNI-2 succinyl- succinate 3 CoA PEPCARBOX-RXN oxaloacetate phosphoenol 2 pyruvate 2OXOGLUTARATEDEH-RXN 2- succinyl- no sequence oxoglutarate CoA

51 4.1.5 Contrasting the Performance of HMM models with and without Clustering 1. Improving overall E-values of the hits We produced two ROC curves to show the dynamics of true positive rate per prediction (Figure 4.13 –similar to Figure 4.8–) and per reaction (Fig- ure 4.14 –similar to Figure 4.9–). For both graphs, the area under the curves increases. This can be used as an evidence of an improved performance.

Figure 4.13: ROC curve (prediction-wise) that used clustered sequences)

2. Increasing the Number of True Positive as well as Identifying iso-enzymes and protein complex In the case of citrate synthase, using the entire training sequences to build one HMM model produced the following result:

P00890: TRUE POSITIVE 3.1e-170 (CIT1) • P08679: TRUE POSITIVE 2.6e-161 (CIT2) • Whereas, prediction using the the optimum cluster number lead to the following result: TRUE POSITIVE: P00890 evalue: 0 (CIT1) • TRUE POSITIVE: P08679 evalue: 3.3e-300 (CIT2) • TRUE POSITIVE: P43635 evalue: 1.1e-191 (CIT3) • Saccharomyces Genome Database (SGD) [2] cited that there are 3 enzymes for citrate synthase, namely CIT1 (P00890), CIT2 (P08679)), and CIT3

52 Figure 4.14: ROC curve (reaction-wise) that used clustered sequences)

Figure 4.15: (left) dendogram for citrate synthase (right) fusion graph for citrate synthase

(P43635). To better illustrate the interaction between these proteins, we borrowed the gene-reaction schematic provided by SGD (Figure 4.16). A gene-reaction schematic is a graph that visualize the relationship among genes, enzymes, and reactions. In gene-reaction schematics, the boxes to the left represent reaction, the boxes to the right represent genes, and the circles in the middle represent polypeptides and protein complexes. The lines indicate relationships among these objects. A line from a circle (a polypeptide) to another circle indicates a protein complex [2]. As ﬁgure 4.16 suggests that there are three proteins for citrate synthase. Since there is no line connecting the circles, these proteins are not known to form a protein complex.

In the case of succinyl-CoA ligase, using the whole training sequences to build one HMM model produced the following hits:

53 Figure 4.16: a gene-reaction schematics for citrate synthase. The reaction is denoted with EC 2.3.3.1. There are three distinct proteins that are able to catalyze this reaction. Each protein is encoded by diﬀerent genes, namely CIT1, CIT2, and CIT3. These three proteins do not form a protein complex.

P53312-TRUE POSITIVE: 1.8e-172 (LSC2) • Whereas, grouping the training sequences into the optimum number of clusters (3) lead to the following results: TRUE POSITIVE: P53312 evalue: 1.4e-191 (LSC2) • TRUE POSITIVE: P53598 evalue: 3.3e-124 (LSC1) •

Figure 4.17: (left) dendogram for succinyl-CoA ligase (right) fusion graph for succinyl-CoA ligase

SGD denoted that succinyl-CoA ligase is a protein complex consisting of two subunits: alpha subunit of succinyl-CoA ligase (LSC1) and beta subunit of succinyl-CoA ligase (LSC2) (Figure 4.18). 3. Finding Novel Hits Using the clustered training sequences produced new hits, which were not found using the non-clusterred training sequences. Two examples of this category are: alpha aminoadipate reductase and aldehyde dehydrogenase. Details of the output for each reaction are as follows:

Alpha aminoadipate reductase result Non- Clustering clustering none P07702 0 True Positive

54 Figure 4.18: a gene-reaction schematics for succinyl-CoA ligase. The reaction is denoted with EC 6.2.1.5. The protein complex consists of two subunits. One subunit is encoded by gene LSC1 and the other is encoded by gene LSC2.

Aldehyde dehydrogenase result Non- Clustering clustering P32872 6.1e-158 False Posi- P32872 1.5e-185 False Posi- tive tive P46367 7e-127 False Posi- P46367 3.2e-172 False Posi- tive tive P40047 8.5e-157 False Posi- tive P54115 8.6e-154 False Posi- tive A9LRZ7 8.6e-154 False Posi- tive P47771 6.8e-142 True Positive P54114 1.3e-137 True Positive

4.1.6 Incorporating maRIboES Predictions into The Re- construction Process We included all maRIboES one-step predictions that satisfy the posterior probability cutoﬀ and hypergeometric test cutoﬀ into the model pathways. If the reaction from compound A to compound B is listed in Metacyc to be catalyzed by enzyme X, whereas maRIboES predicts that enzyme Y can also catalyze the transformation, we denoted the reaction from compound A to compound B can be catalyzed by two enzymes: enzyme X and enzyme Y. In other words, we increased the the size of the training sequences. We also removed the notion of hypothetical true positive, which was introduced in the earlier section, because the concept itself causes confusion. Since the training sequences has changed, thus we recomputed the optimum cluster size for each reaction as we did before. The results are:

Optimum Cluster size calculated via leave-one-out cross validation (or 5-fold cross validation if the number of species exceeds 50)

55 reaction ID product substrate cluster size cluster size (before (after maRI- maRIboES) boES) MALATE-DEH-RXN malate oxaloacetate 9 24 RXNI-3 malate oxaloacetate 2 18 MALATE- malate oxaloacetate 2 18 DEHYDROGENASE- ACCEPTOR-RXN ASPAMINOTRANS-RXN L-aspartate L-glutamate 27 23 + 2- + oxaloac- oxoglutarate etate SUCCCOASYN-RXN succinyl- succinate 3 6 CoA 2-OXOGLUTARATE- 2- succinyl- 3 5 SYNTHASE-RXN oxoglutarate CoA GLUTDEHYD-RXN 2- L-glutamate 2 18 oxoglutarate 2OXOGLUTARATEDEH-RXN 2- succinyl- no sequence True Positive oxoglutarate CoA not found The results of incorporating maRIboES prediction to the reconstruction process are: 1. Sequences that are added based on maRIboES predictions are relatively diﬀerent from the original training sequences This conclusion is derived after doing single-linkage clustering on the new enlarged training sequences. The results are shown in the following dendograms (Figure 4.19, 4.20, 4.21, 4.22, 4.23, 4.24, 4.25, and 4.26). The original metacyc sequences are drawn in blue, whereas the maRIboES inferred sequences are drawn in red.

2. Newly added sequences produce false positive hits Since the newly added sequence has a diﬀerent EC number than the one listed in metacyc, the hits that are found tend to have the new EC number. Thus, these predictions are recognized as false positives. Examples of these category is shown below (Figure 4.27 and 4.28):

56 Figure 4.19: Dendogram for succinyl CoA ligase

Figure 4.20: Dendogram for 2-ketoglutarate dehydrogenase complex (1)

57 Figure 4.21: Dendogram for 2-ketoglutarate dehydrogenase complex (2)

Figure 4.22: Dendogram for aspartate aminotransferase

58 Figure 4.23: Dendogram for Glutamate dehydrogenase (NADP(+))

Figure 4.24: Dendogram for malate dehydrogenase acceptor

59 Figure 4.25: Dendogram for malate dehydrogenase

Figure 4.26: Dendogram for malate quinone oxidoreductase

60 Figure 4.27: Dendogram for The result of the reconstruction process for Gluta- mate dehydrogenase (NADP(+)). Blue lines denote original metacyc sequences. Red lines denote sequences from EC number(s) that maRIboES inferred. The result showed four hits: two are true positives and the rest are false positives

61 Figure 4.28: The result of the reconstruction process for aspartate aminotransferase. The results showed three hits: one true positive and two false positives.

62 Chapter 5

5.1 Determining MaRIboES cut-oﬀ

As opposed to our previous ROC curves that depict the optimum posterior probability cut-off and the hypergeometric test cut-off in different graphs. We combined these cut-offs into one graph and chose the optimum one (denoted in red line). It is shown in figure 5.1.

Figure 5.1: ROC curve that depicts dynamics of true positive rate and false positive rates for every combination of posterior probability and hypergeometric test cut oﬀs..

5.2 Recovering organism-speciﬁc reactions

We build our model pathway by leaving out reactions that can only be found in Saccharomyces cerevisiae. Therefore, these reaction will always be false negatives when we reconstruct our metabolic network. We only ﬁnd enzymes for reactions that are included in the model pathways. By using MaRIboES, we are able to recover these left-out reactions. In other words, we use MaRI- boES to grow our model pathway. Amongst the newly added reactions, are

63 Saccharomyces cerevisiae specific reactions. The EC number that MaRIboES predicted is then used to find the corresponding enzymes. In this way we are able to increase our true positives. Our previous approach is to use MaRIboES to diversify the training sequences for known reaction in model pathway, which yield to unsatisfying results. The current approach is to use MaRIboES to find reactions that are not included in model pathway, but should be there.

We provided examples of such cases:

5.2.1 Isoleucine Degradation In the case of Isoleucine degradation pathway, there are two reactions that are speciﬁc for Saccharomyces cerevisiae (page 69, they are denoted by grey arrows). They are:

The reaction from 2-keto-3-methyl-valerate to 2-methyl butanal. • The reaction from 2-methyl butanal to 2-methyl butanol. • These reactions are left out when we build our model pathway. In other words, our model pathway only consists of those reactions that are denoted by black arrows (page 69). MaRIboES is able to recover one of the two left out reactions (denoted by red arrows). The highest mariboes prediction (EC 1.1.1.1) also matched with the known enzyme to catalyze that reaction (EC 1.1.1.1).

MaRIboES also predicted the reaction from 2-keto-3-methyl-valerate to 2-methyl butanal with the EC number of 1.2.4.4. According to our curated database (metacyc), there is no EC number listed for this reaction. We can derive a conclusion that MaRIboES may also be used to enhance the annotation.

5.2.2 Leucine Degradation In the case of Leucine degradation pathway (page 70), we also recover Sac- charomyces cerevisiae speciﬁc reactions. The left-out reactions are denoted in grey arrows, maRIboES predicted reactions are denoted in red arrows, and the model pathway reactions are denoted in black. Since the recovered reactions are similar with those in Isoleucine degradation pathway, we will not give further explanation.

5.2.3 Methylglyoxal Detoxiﬁcation In this pathway, the Saccharomyces cerevisiae speciﬁc reaction is found between L-Lactate to Pyruvate (denoted in the grey arrow). maRIboES was able to predict the same reaction with the correct EC number as listed in the curated database (metacyc): 1.1.2.3 (denoted in red arrow). This pathway can be found in page 71.

We have shown a new use for MaRIboES predictions. They are used to enrich our model pathways. When maRIboES predicts the correct EC number as listed in the curated database, we are able to ﬁnd the correct enzymes. Thus, we are able to solve gaps and increase our true positive rates.

64 Bibliography

[1] Eddy,R.S. Proﬁle hidden Markov models. Bioinformatics Review Vol. 14 no. 9 1998. Pages 755-765. [2] Nash R, Weng S, Hitz B, Balakrishnan R, Christie KR, Costanzo MC, Dwight SS, Engel SR, Fisk DG, Hirschman JE, Hong EL, Livstone MS, Oughtred R, Park J, Skrzypek M, Theesfeld CL, Binkley G, Dong Q, Lane C, Miyasato S, Sethuraman A, Schroeder M, Dolinski K, Botstein D, Cherry JM (2007) Expanded protein information at SGD: new pages and proteome browser. Nucleic Acids Res 35(Database issue):D468-71

65 4-aminobutyrate

GABATRANSAM-RXN-reactionStatus=TRUE_POSITIVE GABATRANSAM-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-A5H0J7-FALSE_POSITIVE-1.11779e-149 BLAST-A5H0J7-FALSE_POSITIVE-1.11779e-149 BLAST-P17649-TRUE_POSITIVE-5.45571e-149 BLAST-P17649-TRUE_POSITIVE-5.45571e-149 BLAST-P07991-FALSE_POSITIVE-1.80061e-49 BLAST-P07991-FALSE_POSITIVE-1.80061e-49 BLAST-P18544-FALSE_POSITIVE-2.05957e-46 BLAST-P18544-FALSE_POSITIVE-2.05957e-46 HMM-A5H0J7-FALSE_POSITIVE-3.3e-114 HMM-A5H0J7-FALSE_POSITIVE-3.3e-114 HMM-P17649-TRUE_POSITIVE-4.9e-113 HMM-P17649-TRUE_POSITIVE-4.9e-113 HMM-P18544-FALSE_POSITIVE-8.5e-23 HMM-P18544-FALSE_POSITIVE-8.5e-23 HMM-P07991-FALSE_POSITIVE-7.3e-17 HMM-P07991-FALSE_POSITIVE-7.3e-17 HMM-Q5DWF2-FALSE_POSITIVE-7.6e-06 HMM-Q5DWF2-FALSE_POSITIVE-7.6e-06 HMM-Q5DWF5-FALSE_POSITIVE-8e-06 HMM-Q5DWF5-FALSE_POSITIVE-8e-06 HMM-Q4R1J2-FALSE_POSITIVE-1.7e-05 HMM-Q4R1J2-FALSE_POSITIVE-1.7e-05 HMM-Q4R1J1-FALSE_POSITIVE-0.0002 HMM-Q4R1J1-FALSE_POSITIVE-0.0002 HMM-Q66R22-FALSE_POSITIVE-0.00021 HMM-Q66R22-FALSE_POSITIVE-0.00021 HMM-P50277-FALSE_POSITIVE-0.00021 HMM-P50277-FALSE_POSITIVE-0.00021

L-glutamate succinate semialdehyde

SUCCINATE-SEMIALDEHYDE-DEHYDROGENASE-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P38067-FALSE_POSITIVE-4.47258e-121 BLAST-P40047-FALSE_POSITIVE-1.76554e-75 BLAST-P46367-FALSE_POSITIVE-2.32721e-72 BLAST-P54115-FALSE_POSITIVE-1.10018e-66 BLAST-A9LRZ7-FALSE_POSITIVE-1.10018e-66 BLAST-P32872-FALSE_POSITIVE-9.79171e-66 BLAST-P47771-FALSE_POSITIVE-4.62765e-61 BLAST-P54114-FALSE_POSITIVE-6.19888e-60 BLAST-P38694-FALSE_POSITIVE-4.23899e-47 HMM-P38067-FALSE_POSITIVE-6.1e-151 HMM-P40047-FALSE_POSITIVE-1.7e-77 GLUTAMATE-DEHYDROGENASE-RXN-reactionStatus=TRUE_POSITIVE HMM-P46367-FALSE_POSITIVE-7.7e-67 MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE List of predictions: HMM-A9LRZ7-FALSE_POSITIVE-4.5e-48 List of predictions: List of predictions: BLAST-P33327-TRUE_POSITIVE-0 HMM-P54115-FALSE_POSITIVE-4.5e-48 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P07262-FALSE_POSITIVE-1.05556e-110 HMM-P32872-FALSE_POSITIVE-2.9e-42 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE BLAST-P39708-FALSE_POSITIVE-1.80156e-108 4-HYDROXYBUTYRATE-DEHYDROGENASE-RXN-reactionStatus=FALSE_NEGATIVE HMM-P47771-FALSE_POSITIVE-1.9e-37 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P47176-TRUE_POSITIVE-3.7e-162 BLAST-P39703-FALSE_POSITIVE-7.50934e-61 HMM-P54114-FALSE_POSITIVE-1.7e-36 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P07262-FALSE_POSITIVE-1e-151 HMM-P38694-FALSE_POSITIVE-7.3e-16 HMM-P39708-FALSE_POSITIVE-8.7e-149 HMM-P07275-FALSE_POSITIVE-6.8e-08 HMM-Q04458-FALSE_POSITIVE-1.5e-06 HMM-P22281-FALSE_POSITIVE-0.00017

SUCCSEMIALDDEHYDROG-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P38067-TRUE_POSITIVE-2.1398e-148 BLAST-P40047-FALSE_POSITIVE-1.21204e-94 BLAST-P46367-FALSE_POSITIVE-4.32337e-82 BLAST-P47771-FALSE_POSITIVE-1.31226e-79 BLAST-P54114-FALSE_POSITIVE-1.84752e-79 BLAST-A9LRZ7-FALSE_POSITIVE-8.5132e-76 BLAST-P54115-FALSE_POSITIVE-8.5132e-76 BLAST-P32872-FALSE_POSITIVE-4.37225e-72

2-oxoglutarate N-acetyl-L-glutamate ammonia 4-hydroxybutyrate succinate

RXN-8889-reactionStatus=TRUE_NEGATIVE RXN-8889-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE

4-hydroxybutyryl-CoA acetate succinyl-CoA

MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE

MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 RXN-8890-reactionStatus=TRUE_NEGATIVE BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-6.6e-09 HMM-P38137-FALSE_POSITIVE-6.6e-09

vinylacetyl-CoA acetyl-CoA

VINYLACETYL-COA-DELTA-ISOMERASE-RXN-reactionStatus=FALSE_NEGATIVE

crotonyl-CoA R11-RXN-reactionStatus=FALSE_NEGATIVE

R22-RXN-reactionStatus=FALSE_NEGATIVE

butyryl-CoA

R11-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: List of predictions: List of predictions: BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P32473-FALSE_POSITIVE-1.1e-55 BLAST-P52910-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P16387-FALSE_POSITIVE-1.5e-12 HMM-P16387-FALSE_POSITIVE-1.5e-12 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-6.6e-09 HMM-P38137-FALSE_POSITIVE-6.6e-09

2-ketopentanoate butyrate

Pathway ID: 4-Aminobutyraye-Degradation-Saccharomyces cerevisiae 4-hydroxyphenylpyruvate

HYDROXYPHENYLPYRUVATE-REDUCTASE-RXN-reactionStatus=TRUE_NEGATIVE

4-hydroxyphenyllactate

RXN3O-1118-reactionStatus=TRUE_NEGATIVE

4-coumarate

4-COUMARATE--COA-LIGASE-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-P38137-FALSE_POSITIVE-5.5e-10 HMM-P52910-FALSE_POSITIVE-1.6e-08 HMM-P39518-FALSE_POSITIVE-2.9e-08 HMM-Q01574-FALSE_POSITIVE-7.4e-08 HMM-Q66RJ0-FALSE_POSITIVE-1.1e-07 HMM-P30624-FALSE_POSITIVE-6e-05 HMM-P38225-FALSE_POSITIVE-0.0001 HMM-P47912-FALSE_POSITIVE-0.00011 HMM-P39002-FALSE_POSITIVE-0.00014

4-coumaroyl-CoA

RXN3O-1120-reactionStatus=TRUE_NEGATIVE

4-hydroxybenzoyl-CoA chorismate

CHORPYRLY-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-Q02981-FALSE_POSITIVE-2.7e-10 3.1.2.23-RXN-reactionStatus=FALSE_NEGATIVE HMM-Q06567-FALSE_POSITIVE-1.3e-08 HMM-P27697-FALSE_POSITIVE-1.8e-06

4-hydroxybenzoate

Pathway ID: 4-Hydroxybenzoate-Biosynthesis-Saccharomyces cerevisiae urate

RXN0-5473-reactionStatus=TRUE_NEGATIVE

S-allantoin

ALLANTOINASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P32375-TRUE_POSITIVE-3.26944e-85 HMM-P32375-TRUE_POSITIVE-1.8e-78

allantoate

ALLANTOATE-DEIMINASE-RXN-reactionStatus=FALSE_NEGATIVE

ALLANTOICASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: ureidoglycine BLAST-P25335-TRUE_POSITIVE-9.09192e-97 HMM-P25335-TRUE_POSITIVE-8.8e-129

URUR-RXN-reactionStatus=TRUE_NEGATIVE

S-ureidoglycolate

Pathway ID: Allantoin-degradation-Saccharomyces cerevisiae L-arginine

ARG-OXIDATION-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: ARGINASE-RXN-reactionStatus=TRUE_POSITIVE ARGDECARBOX-RXN-reactionStatus=FALSE_NEGATIVE HMM-Q04471-FALSE_POSITIVE-1.2e-08 List of predictions: List of predictions: ARGININE-N-SUCCINYLTRANSFERASE-RXN-reactionStatus=FALSE_NEGATIVE ARGININE-2-MONOOXYGENASE-RXN-reactionStatus=TRUE_NEGATIVE ARGININE-DEIMINASE-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P00812-TRUE_POSITIVE-4.4499e-123 BLAST-P08432-FALSE_POSITIVE-1.83253e-69 RXN-7564-reactionStatus=TRUE_NEGATIVE HMM-P00812-TRUE_POSITIVE-1.5e-82 HMM-P08432-FALSE_POSITIVE-1.1e-45

RXN-8956-reactionStatus=TRUE_NEGATIVE

2-ketoarginine L-citrulline urea agmatine

ARGINASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: N2-succinyl-L-arginine 4-guanidinobutyramide 4.1.1.75-RXN-reactionStatus=TRUE_NEGATIVERXN-7565-reactionStatus=TRUE_NEGATIVE BLAST-P00812-TRUE_POSITIVE-4.4499e-123 MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE AGMATINE-DEIMINASE-RXN-reactionStatus=FALSE_NEGATIVE HMM-P00812-TRUE_POSITIVE-1.5e-82

GUANIDINOBUTANAMIDE-NH3-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P02557-FALSE_POSITIVE-5.64997e-154 BLAST-B7TJ96-FALSE_POSITIVE-2.23794e-125 ORNCARBAMTRANSFER-RXN-reactionStatus=TRUE_POSITIVE BLAST-P38318-FALSE_POSITIVE-1.50208e-82 List of predictions: AGMATIN-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P09733-FALSE_POSITIVE-2.49105e-72 BLAST-P05150-TRUE_POSITIVE-1.58385e-97 List of predictions: SUCCARGDIHYDRO-RXN-reactionStatus=FALSE_NEGATIVE 4-guanidinobutyraldehyde 2-keto-ornithine N-acetyl-L-citrulline N-carbamoylputrescine BLAST-P09734-FALSE_POSITIVE-2.51338e-70 HMM-P05150-TRUE_POSITIVE-6.8e-135 HMM-P00812-FALSE_POSITIVE-6.5e-06 BLAST-P22580-TRUE_POSITIVE-3.40362e-56 HMM-P07259-FALSE_POSITIVE-1.1e-21 HMM-P22580-TRUE_POSITIVE-1.9e-65 HMM-P32528-FALSE_POSITIVE-1.2e-11 HMM-Q03557-FALSE_POSITIVE-0.00049

MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE N-CARBAMOYLPUTRESCINE-AMIDASE-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: List of predictions: List of predictions: BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 HMM-P49954-FALSE_POSITIVE-4.9e-08 1.2.1.54-RXN-reactionStatus=TRUE_NEGATIVEBLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-Q71SP9-FALSE_POSITIVE-4.9e-08 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P47016-FALSE_POSITIVE-2.8e-05 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-Q71SQ0-FALSE_POSITIVE-2.8e-05

N2-succinyl-L-ornithine 4-guanidinobutyrate L-ornithine putrescine

SUCCORNTRANSAM-RXN-reactionStatus=FALSE_NEGATIVE ORNITHINE-GLU-AMINOTRANSFORASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P18544-FALSE_POSITIVE-5.90798e-80 BLAST-P07991-TRUE_POSITIVE-8.42346e-142 BLAST-P07991-FALSE_POSITIVE-2.75952e-58 BLAST-P18544-FALSE_POSITIVE-6.21927e-56 HMM-P18544-FALSE_POSITIVE-6.6e-104 HMM-P07991-TRUE_POSITIVE-1.9e-247 MARIBOES-2.5.1.16-RXN-reactionStatus=TRUE_POSITIVE HMM-P07991-FALSE_POSITIVE-2.5e-67 HMM-P18544-FALSE_POSITIVE-1.1e-26 List of predictions: HMM-Q5DWF2-FALSE_POSITIVE-4.3e-08 HMM-Q5DWF5-FALSE_POSITIVE-1.1e-14 BLAST-Q12074-TRUE_POSITIVE-7.56503e-124 HMM-Q4R1J1-FALSE_POSITIVE-4.4e-08 GUANIDINOBUTYRASE-RXN-reactionStatus=FALSE_NEGATIVE HMM-Q5DWF2-FALSE_POSITIVE-1.4e-14 MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE ORNITHINE-RACEMASE-RXN-reactionStatus=FALSE_NEGATIVE BLAST-Q12455-FALSE_POSITIVE-6.26985e-81 HMM-Q5DWF5-FALSE_POSITIVE-5.3e-08 HMM-Q4R1J2-FALSE_POSITIVE-9.2e-14 HMM-Q12074-TRUE_POSITIVE-6.4e-137 HMM-P50277-FALSE_POSITIVE-5.5e-08 HMM-P50277-FALSE_POSITIVE-4.5e-12 HMM-Q12455-FALSE_POSITIVE-3.8e-116 HMM-Q66R22-FALSE_POSITIVE-6e-08 HMM-Q66R22-FALSE_POSITIVE-5.4e-12 HMM-Q4R1J2-FALSE_POSITIVE-6.5e-08 HMM-Q4R1J1-FALSE_POSITIVE-6.1e-12 HMM-P17649-FALSE_POSITIVE-9.2e-07 HMM-P17649-FALSE_POSITIVE-8.5e-11 HMM-A5H0J7-FALSE_POSITIVE-9.2e-07 HMM-A5H0J7-FALSE_POSITIVE-1e-10

N2-succinyl-L-glutamate 5-semialdehyde 4-aminobutyrate L-glutamate γ-semialdehyde N-acetyl-L-ornithine D-ornithine spermidine

SUCCGLUALDDEHYD-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P40047-FALSE_POSITIVE-2.2075e-55 BLAST-P38067-FALSE_POSITIVE-2.61142e-51 SUCCORNTRANSAM-RXN-reactionStatus=FALSE_NEGATIVE ORNITHINE-GLU-AMINOTRANSFORASE-RXN-reactionStatus=TRUE_POSITIVE BLAST-P46367-FALSE_POSITIVE-1.18306e-48 List of predictions: List of predictions: BLAST-P47771-FALSE_POSITIVE-2.36467e-48 BLAST-P18544-FALSE_POSITIVE-5.90798e-80 BLAST-P07991-TRUE_POSITIVE-8.42346e-142 BLAST-P54114-FALSE_POSITIVE-7.05453e-48 BLAST-P07991-FALSE_POSITIVE-2.75952e-58 BLAST-P18544-FALSE_POSITIVE-6.21927e-56 BLAST-A9LRZ7-FALSE_POSITIVE-1.2673e-41 HMM-P18544-FALSE_POSITIVE-6.6e-104 HMM-P07991-TRUE_POSITIVE-1.9e-247 BLAST-P54115-FALSE_POSITIVE-1.2673e-41 HMM-P07991-FALSE_POSITIVE-2.5e-67 HMM-P18544-FALSE_POSITIVE-1.1e-26 BLAST-P32872-FALSE_POSITIVE-1.68299e-41 HMM-Q5DWF2-FALSE_POSITIVE-4.3e-08 HMM-Q5DWF5-FALSE_POSITIVE-1.1e-14 HMM-P40047-FALSE_POSITIVE-2.9e-53 HMM-Q4R1J1-FALSE_POSITIVE-4.4e-08 HMM-Q5DWF2-FALSE_POSITIVE-1.4e-14 MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE SPONTPRO-RXN-reactionStatus=TRUE_NEGATIVE ORNITHINE-CYCLODEAMINASE-RXN-reactionStatus=FALSE_NEGATIVE ORNMUTST-RXN-reactionStatus=TRUE_NEGATIVE HMM-P38067-FALSE_POSITIVE-2.9e-46 HMM-Q5DWF5-FALSE_POSITIVE-5.3e-08 HMM-Q4R1J2-FALSE_POSITIVE-9.2e-14 HMM-P46367-FALSE_POSITIVE-1.5e-42 HMM-P50277-FALSE_POSITIVE-5.5e-08 HMM-P50277-FALSE_POSITIVE-4.5e-12 HMM-P54114-FALSE_POSITIVE-8.8e-35 HMM-Q66R22-FALSE_POSITIVE-6e-08 HMM-Q66R22-FALSE_POSITIVE-5.4e-12 HMM-P47771-FALSE_POSITIVE-7.4e-34 HMM-Q4R1J2-FALSE_POSITIVE-6.5e-08 HMM-Q4R1J1-FALSE_POSITIVE-6.1e-12 HMM-P54115-FALSE_POSITIVE-1.7e-31 HMM-P17649-FALSE_POSITIVE-9.2e-07 HMM-P17649-FALSE_POSITIVE-8.5e-11 HMM-A9LRZ7-FALSE_POSITIVE-1.7e-31 HMM-A5H0J7-FALSE_POSITIVE-9.2e-07 HMM-A5H0J7-FALSE_POSITIVE-1e-10 HMM-P32872-FALSE_POSITIVE-2e-16 HMM-P07275-FALSE_POSITIVE-2.3e-14 HMM-P38694-FALSE_POSITIVE-2.6e-13 HMM-Q04458-FALSE_POSITIVE-1.5e-12

N2-succinylglutamate N-acetyl-L-glutamate 5-semialdehyde (S)-1-pyrroline-5-carboxylate 2,4-diaminopentanoate

PYRROLINECARBDEHYDROG-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P07275-TRUE_POSITIVE-3.03652e-156 BLAST-P40047-FALSE_POSITIVE-1.02785e-71 BLAST-P46367-FALSE_POSITIVE-7.60239e-68 BLAST-P47771-FALSE_POSITIVE-7.73032e-68 BLAST-P54114-FALSE_POSITIVE-5.97022e-67 BLAST-A9LRZ7-FALSE_POSITIVE-2.49413e-64 BLAST-P54115-FALSE_POSITIVE-2.49413e-64 BLAST-P32872-FALSE_POSITIVE-5.98755e-57 BLAST-P38067-FALSE_POSITIVE-8.30958e-49 PYRROLINECARBREDUCT-RXN-reactionStatus=TRUE_POSITIVE HMM-P07275-TRUE_POSITIVE-7e-243 List of predictions: SUCCGLUDESUCC-RXN-reactionStatus=FALSE_NEGATIVE SUCCGLUDESUCC-RXN-reactionStatus=FALSE_NEGATIVE 24-DIAMINOPENTANOATE-DEHYDROGENASE-RXN-reactionStatus=TRUE_NEGATIVE HMM-P40047-FALSE_POSITIVE-5.6e-72 HMM-P32263-TRUE_POSITIVE-1.3e-32 HMM-P46367-FALSE_POSITIVE-1.5e-71 HMM-P54114-FALSE_POSITIVE-2.7e-62 HMM-P54115-FALSE_POSITIVE-4.9e-62 HMM-A9LRZ7-FALSE_POSITIVE-4.9e-62 HMM-P47771-FALSE_POSITIVE-8.8e-61 HMM-P32872-FALSE_POSITIVE-3.3e-39 HMM-P38067-FALSE_POSITIVE-2.3e-17 HMM-P38694-FALSE_POSITIVE-1.9e-15 HMM-Q04458-FALSE_POSITIVE-6.1e-10 HMM-P22281-FALSE_POSITIVE-1.4e-06

succinate L-glutamate L-proline 2-amino-4-oxopentanoate

MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE PROLINE-RACEMASE-RXN-reactionStatus=FALSE_NEGATIVE AKPTHIOL-RXN-reactionStatus=TRUE_NEGATIVE HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P38891-TRUE_POSITIVE-7.5e-157

succinyl-CoA 2-oxoglutarate N-acetyl-L-glutamate D-proline D-alanine

PRDABST-RXN-reactionStatus=FALSE_NEGATIVE

5-aminopentanoate

Pathway ID: ARGININE-DEG-Saccharomyces cerevisiae L-glutamine

CARBPSYN-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P07259-TRUE_POSITIVE-0 BLAST-P03965-TRUE_POSITIVE-0 BLAST-P07258-TRUE_POSITIVE-3.05627e-147 HMM-P03965-TRUE_POSITIVE-0 HMM-P07259-TRUE_POSITIVE-0 HMM-P07258-TRUE_POSITIVE-1.2e-173

L-glutamate

ACETYLORNTRANSAM-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P18544-TRUE_POSITIVE-0 BLAST-P07991-FALSE_POSITIVE-1.53509e-105 HMM-P18544-TRUE_POSITIVE-1.7e-211 HMM-P07991-FALSE_POSITIVE-2.4e-150 HMM-Q5DWF5-FALSE_POSITIVE-3.6e-22 HMM-Q5DWF2-FALSE_POSITIVE-4.4e-22 HMM-Q4R1J2-FALSE_POSITIVE-2.1e-21 HMM-P50277-FALSE_POSITIVE-5.3e-20 HMM-Q4R1J1-FALSE_POSITIVE-5.9e-20 HMM-Q66R22-FALSE_POSITIVE-1e-19 HMM-P17649-FALSE_POSITIVE-1.9e-16 HMM-A5H0J7-FALSE_POSITIVE-2.2e-16

N-ACETYLTRANSFER-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-Q04728-TRUE_POSITIVE-2.77086e-75 HMM-Q04728-TRUE_POSITIVE-9.4e-165 HMM-Q01217-FALSE_POSITIVE-2.9e-08

MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE N-acetyl-L-ornithine GLUTAMATE-N-ACETYLTRANSFERASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-Q04728-TRUE_POSITIVE-2.77086e-75 HMM-Q04728-TRUE_POSITIVE-1.6e-129

MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE

GLUTAMATE-N-ACETYLTRANSFERASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-Q04728-TRUE_POSITIVE-2.77086e-75 HMM-Q04728-TRUE_POSITIVE-1.6e-129

N-acetyl-L-glutamate

ACETYLORNTRANSAM-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P18544-TRUE_POSITIVE-0 BLAST-P07991-FALSE_POSITIVE-1.53509e-105 CARBPSYN-RXN-reactionStatus=TRUE_POSITIVE HMM-P18544-TRUE_POSITIVE-1.7e-211 List of predictions: ACETYLGLUTKIN-RXN-reactionStatus=TRUE_POSITIVE HMM-P07991-FALSE_POSITIVE-2.4e-150 BLAST-P07259-TRUE_POSITIVE-0 List of predictions: HMM-Q5DWF5-FALSE_POSITIVE-3.6e-22 BLAST-P03965-TRUE_POSITIVE-0 PROLINE-MULTI-reactionStatus=TRUE_NEGATIVE BLAST-Q01217-TRUE_POSITIVE-0 HMM-Q5DWF2-FALSE_POSITIVE-4.4e-22 BLAST-P07258-TRUE_POSITIVE-3.05627e-147 HMM-Q01217-TRUE_POSITIVE-0 HMM-Q4R1J2-FALSE_POSITIVE-2.1e-21 HMM-P03965-TRUE_POSITIVE-0 HMM-P50277-FALSE_POSITIVE-5.3e-20 HMM-P07259-TRUE_POSITIVE-0 HMM-Q4R1J1-FALSE_POSITIVE-5.9e-20 HMM-P07258-TRUE_POSITIVE-1.2e-173 HMM-Q66R22-FALSE_POSITIVE-1e-19 HMM-P17649-FALSE_POSITIVE-1.9e-16 HMM-A5H0J7-FALSE_POSITIVE-2.2e-16

ORNITHINE-GLU-AMINOTRANSFORASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: ORNITHINE-GLU-AMINOTRANSFORASE-RXN-reactionStatus=TRUE_POSITIVE BLAST-P07991-TRUE_POSITIVE-8.42346e-142 List of predictions: BLAST-P18544-FALSE_POSITIVE-6.21927e-56 BLAST-P07991-TRUE_POSITIVE-8.42346e-142 HMM-P07991-TRUE_POSITIVE-1.9e-247 GLUTAMATE-DEHYDROGENASE-NADP+-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P18544-FALSE_POSITIVE-6.21927e-56 HMM-P18544-FALSE_POSITIVE-3.8e-26 List of predictions: HMM-P07991-TRUE_POSITIVE-1.9e-247 HMM-Q5DWF5-FALSE_POSITIVE-2.4e-14 BLAST-P07262-FALSE_POSITIVE-8.66749e-119 HMM-P18544-FALSE_POSITIVE-3.8e-26 HMM-Q5DWF2-FALSE_POSITIVE-3.1e-14 BLAST-P39708-FALSE_POSITIVE-1.27301e-116 HMM-Q5DWF5-FALSE_POSITIVE-2.4e-14 HMM-Q4R1J2-FALSE_POSITIVE-2e-13 HMM-P07262-FALSE_POSITIVE-8e-122 HMM-Q5DWF2-FALSE_POSITIVE-3.1e-14 HMM-P50277-FALSE_POSITIVE-9.2e-12 HMM-P39708-FALSE_POSITIVE-1.3e-118 HMM-Q4R1J2-FALSE_POSITIVE-2e-13 HMM-Q66R22-FALSE_POSITIVE-1.1e-11 HMM-P50277-FALSE_POSITIVE-9.2e-12 HMM-Q4R1J1-FALSE_POSITIVE-1.2e-11 N-acetylglutamyl-phosphate HMM-Q66R22-FALSE_POSITIVE-1.1e-11 HMM-P17649-FALSE_POSITIVE-1.7e-10 MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE HMM-Q4R1J1-FALSE_POSITIVE-1.2e-11 HMM-A5H0J7-FALSE_POSITIVE-2e-10 List of predictions: HMM-P17649-FALSE_POSITIVE-1.7e-10 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 HMM-A5H0J7-FALSE_POSITIVE-2e-10 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE HMM-P47176-TRUE_POSITIVE-3.7e-162 List of predictions: HMM-P38891-TRUE_POSITIVE-7.5e-157 GLUTAMATE-N-ACETYLTRANSFERASE-RXN-reactionStatus=TRUE_POSITIVE BLAST-P47176-TRUE_POSITIVE-1.49811e-110 List of predictions: BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-Q04728-TRUE_POSITIVE-2.77086e-75 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-Q04728-TRUE_POSITIVE-1.6e-129 HMM-P38891-TRUE_POSITIVE-7.5e-157

N-ACETYLGLUTPREDUCT-RXN-reactionStatus=TRUE_POSITIVE GLUTAMATE-N-ACETYLTRANSFERASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-Q01217-TRUE_POSITIVE-0 MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE BLAST-Q04728-TRUE_POSITIVE-2.77086e-75 HMM-Q01217-TRUE_POSITIVE-0 HMM-Q04728-TRUE_POSITIVE-1.6e-129 HMM-P13663-FALSE_POSITIVE-4.2e-06

L-glutamate-5-phosphate N-acetyl-L-glutamate 5-semialdehyde

2.1.3.9-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE HMM-P05150-FALSE_POSITIVE-4.6e-06

L-glutamate γ-semialdehyde

ORNITHINE-GLU-AMINOTRANSFORASE-RXN-reactionStatus=TRUE_POSITIVE ORNITHINE-GLU-AMINOTRANSFORASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P07991-TRUE_POSITIVE-8.42346e-142 BLAST-P07991-TRUE_POSITIVE-8.42346e-142 BLAST-P18544-FALSE_POSITIVE-6.21927e-56 BLAST-P18544-FALSE_POSITIVE-6.21927e-56 HMM-P07991-TRUE_POSITIVE-1.9e-247 HMM-P07991-TRUE_POSITIVE-1.9e-247 HMM-P18544-FALSE_POSITIVE-3.8e-26 HMM-P18544-FALSE_POSITIVE-3.8e-26 HMM-Q5DWF5-FALSE_POSITIVE-2.4e-14 HMM-Q5DWF5-FALSE_POSITIVE-2.4e-14 HMM-Q5DWF2-FALSE_POSITIVE-3.1e-14 HMM-Q5DWF2-FALSE_POSITIVE-3.1e-14 HMM-Q4R1J2-FALSE_POSITIVE-2e-13 HMM-Q4R1J2-FALSE_POSITIVE-2e-13 HMM-P50277-FALSE_POSITIVE-9.2e-12 HMM-P50277-FALSE_POSITIVE-9.2e-12 HMM-Q66R22-FALSE_POSITIVE-1.1e-11 HMM-Q66R22-FALSE_POSITIVE-1.1e-11 HMM-Q4R1J1-FALSE_POSITIVE-1.2e-11 HMM-Q4R1J1-FALSE_POSITIVE-1.2e-11 HMM-P17649-FALSE_POSITIVE-1.7e-10 HMM-P17649-FALSE_POSITIVE-1.7e-10 HMM-A5H0J7-FALSE_POSITIVE-2e-10 HMM-A5H0J7-FALSE_POSITIVE-2e-10

2-oxoglutarate L-ornithine carbamoyl-phosphate

MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE ORNCARBAMTRANSFER-RXN-reactionStatus=TRUE_POSITIVE ORNCARBAMTRANSFER-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: List of predictions: List of predictions: BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P05150-TRUE_POSITIVE-1.58385e-97 BLAST-P05150-TRUE_POSITIVE-1.58385e-97 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-P05150-TRUE_POSITIVE-6.8e-135 HMM-P05150-TRUE_POSITIVE-6.8e-135 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P07259-FALSE_POSITIVE-6.2e-25 HMM-P07259-FALSE_POSITIVE-6.2e-25 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P38891-TRUE_POSITIVE-7.5e-157

2.1.3.9-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: 2-keto-ornithine L-citrulline HMM-P05150-FALSE_POSITIVE-4.6e-06

ARGSUCCINSYN-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P22768-TRUE_POSITIVE-2.91905e-145 RXN-7933-reactionStatus=FALSE_NEGATIVE MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE HMM-P22768-TRUE_POSITIVE-6.4e-188

NITRIC-OXIDE-SYNTHASE-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-P16603-FALSE_POSITIVE-2.7e-08 HMM-P39692-FALSE_POSITIVE-3.4e-07 HMM-A0SXI5-FALSE_POSITIVE-3.8e-07 HMM-A0SXI6-FALSE_POSITIVE-3.9e-07 HMM-A0SXJ0-FALSE_POSITIVE-3.9e-07 L-arginino-succinate HMM-A0SXJ1-FALSE_POSITIVE-4e-07 N-acetyl-L-citrulline HMM-B6SEV8-FALSE_POSITIVE-4.2e-07 HMM-A0SXI4-FALSE_POSITIVE-4.7e-07 HMM-A0SXI7-FALSE_POSITIVE-5.1e-07 HMM-B6SEV9-FALSE_POSITIVE-5.6e-07 HMM-A0SXI9-FALSE_POSITIVE-6.8e-07 HMM-Q12181-FALSE_POSITIVE-7.1e-05

ARGSUCCINLYA-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P04076-TRUE_POSITIVE-0 HMM-P04076-TRUE_POSITIVE-2.1e-274

L-arginine

Pathway ID: ARGININE-SYN-Saccharomyces cerevisiae hydrogen cyanide L-cysteine

L-3-CYANOALANINE-SYNTHASE-RXN-reactionStatus=TRUE_NEGATIVE L-3-CYANOALANINE-SYNTHASE-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE

3-cyano-L-alanine N-acetyl-L-cysteine

3.5.5.4-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P40447-FALSE_POSITIVE-2.68275e-54 HMM-P40447-FALSE_POSITIVE-6.7e-10

3-CYANOALANINE-HYDRATASE-RXN-reactionStatus=TRUE_NEGATIVE L-aspartate

ASNSYNB-RXN-reactionStatus=TRUE_POSITIVE List of predictions: RXN490-3616-reactionStatus=TRUE_NEGATIVE BLAST-Q6B272-FALSE_POSITIVE-0 MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE BLAST-P49090-TRUE_POSITIVE-0 List of predictions: List of predictions: MARIBOES-6.1.1.11-RXN-reactionStatus=TRUE_POSITIVE BLAST-P49089-TRUE_POSITIVE-1.1549e-154 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 List of predictions: HMM-P49090-TRUE_POSITIVE-1.4e-220 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P07284-TRUE_POSITIVE-0 HMM-P49089-TRUE_POSITIVE-6.2e-220 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P47176-TRUE_POSITIVE-3.7e-162 BLAST-P38705-TRUE_POSITIVE-1.40506e-74 HMM-Q6B272-FALSE_POSITIVE-1.3e-219 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P07284-TRUE_POSITIVE-1e-156 HMM-P38705-TRUE_POSITIVE-2.1e-91

ASNSYNA-RXN-reactionStatus=FALSE_NEGATIVE

L-asparagine oxaloacetate L-aspartyl-tRNAAsn

RXN490-3617-reactionStatus=TRUE_NEGATIVE

MARIBOES-2.7.1.11-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P16861-TRUE_POSITIVE-0 BLAST-P16862-TRUE_POSITIVE-0 HMM-P16861-TRUE_POSITIVE-0 HMM-P16862-TRUE_POSITIVE-0

MARIBOES-2.7.1.36-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P07277-TRUE_POSITIVE-9.45064e-41 HMM-P07277-TRUE_POSITIVE-6.9e-47

MARIBOES-2.7.1.49-RXN-reactionStatus=TRUE_NEGATIVE

MARIBOES-2.7.1.86-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P32622-FALSE_POSITIVE-5.84898e-67 BLAST-P21373-FALSE_POSITIVE-6.57563e-66 BLAST-Q6B231-FALSE_POSITIVE-1.68814e-65

MARIBOES-2.7.2.3-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P00560-TRUE_POSITIVE-0 HMM-P00560-TRUE_POSITIVE-1.4e-247

MARIBOES-2.7.4.9-RXN-reactionStatus=TRUE_POSITIVE List of predictions: HMM-P00572-TRUE_POSITIVE-1.6e-29

MARIBOES-3.1.3.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P11491-TRUE_POSITIVE-4.33135e-102 BLAST-Q66RD0-FALSE_POSITIVE-1.28731e-49 HMM-P11491-TRUE_POSITIVE-8.1e-29 HMM-Q66RD0-FALSE_POSITIVE-1.8e-28

MARIBOES-3.6.1.15-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P40009-FALSE_POSITIVE-2.34511e-60 HMM-P32628-FALSE_POSITIVE-1.8e-43 HMM-P40009-FALSE_POSITIVE-4.4e-24 HMM-P47119-FALSE_POSITIVE-5.8e-22 HMM-P32621-FALSE_POSITIVE-1.4e-11 HMM-Q05131-FALSE_POSITIVE-5.1e-10

MARIBOES-3.6.3.43-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P40416-FALSE_POSITIVE-3.82724e-67 BLAST-P33311-FALSE_POSITIVE-3.34714e-57 BLAST-P33310-FALSE_POSITIVE-1.90007e-53 BLAST-P12866-FALSE_POSITIVE-3.02041e-49 BLAST-P38735-FALSE_POSITIVE-3.40255e-41 HMM-P40416-FALSE_POSITIVE-9.1e-25 HMM-P33311-FALSE_POSITIVE-1.4e-11

Charged-ASN-tRNAs

Pathway ID: ASPARAGINE-SYN-Saccharomyces cerevisiae L-aspartate

ASPAMINOTRANS-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P23542-TRUE_POSITIVE-1.11445e-106 BLAST-Q01802-TRUE_POSITIVE-1.34166e-73 HMM-P23542-TRUE_POSITIVE-5.7e-143 HMM-Q01802-TRUE_POSITIVE-7.1e-74 HMM-P47039-FALSE_POSITIVE-2e-32 MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE HMM-P52892-FALSE_POSITIVE-9.6e-10 List of predictions: HMM-Q66RF8-FALSE_POSITIVE-1.5e-09 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 HMM-P52893-FALSE_POSITIVE-2e-09 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P38891-TRUE_POSITIVE-7.5e-157 MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P38891-TRUE_POSITIVE-7.5e-157

oxaloacetate

MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P00175-TRUE_POSITIVE-5.46824e-166 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-Q07540-FALSE_POSITIVE-2.1e-08

malate

Pathway ID: ASPARTATE-DEG-Saccharomyces cerevisiae putrescine propionyl-CoA

PROPIONATE--COA-LIGASE-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-Q01574-FALSE_POSITIVE-6.00122e-119 BLAST-Q66RJ0-FALSE_POSITIVE-1.61977e-118 BLAST-P52910-FALSE_POSITIVE-2.32153e-114 MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE HMM-Q01574-FALSE_POSITIVE-4.8e-130 HMM-Q66RJ0-FALSE_POSITIVE-5.7e-129 MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-2.5.1.16-RXN-reactionStatus=TRUE_POSITIVE HMM-P52910-FALSE_POSITIVE-1.1e-124 MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: List of predictions: List of predictions: List of predictions: BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q12074-TRUE_POSITIVE-7.56503e-124 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P52910-TRUE_POSITIVE-0 MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE BLAST-Q12455-FALSE_POSITIVE-6.26985e-81 PROPCOASYN-RXN-reactionStatus=FALSE_NEGATIVE HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P32473-FALSE_POSITIVE-1.1e-55 BLAST-Q01574-TRUE_POSITIVE-0 HMM-Q12074-TRUE_POSITIVE-6.4e-137 HMM-P16387-FALSE_POSITIVE-1.2e-12 HMM-P16387-FALSE_POSITIVE-1.2e-12 HMM-P52910-TRUE_POSITIVE-0 MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE HMM-Q12455-FALSE_POSITIVE-3.8e-116 HMM-Q01574-TRUE_POSITIVE-0 List of predictions: HMM-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-8.4e-10 BLAST-P52910-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-8.4e-10

spermidine 2-oxobutanoate propionate acrylyl-CoA

RXN-6383-reactionStatus=FALSE_NEGATIVE List of predictions: MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE HMM-P53196-FALSE_POSITIVE-7.5e-13 MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE HMM-P28817-FALSE_POSITIVE-1.6e-10 List of predictions: MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-2.5.1.16-RXN-reactionStatus=TRUE_POSITIVE HMM-Q08558-FALSE_POSITIVE-6.4e-06 BLAST-Q66RJ0-FALSE_POSITIVE-0 List of predictions: List of predictions: HMM-Q05871-FALSE_POSITIVE-1e-05 BLAST-P52910-TRUE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q12074-TRUE_POSITIVE-7.56503e-124 HMM-Q05946-FALSE_POSITIVE-4.1e-05 BLAST-Q01574-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-Q12455-FALSE_POSITIVE-6.26985e-81 SPERMIDINE-DEHYDROGENASE-RXN-reactionStatus=FALSE_NEGATIVE HMM-P47025-FALSE_POSITIVE-9.2e-05 HMM-P52910-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-Q12074-TRUE_POSITIVE-6.4e-137 HMM-P16649-FALSE_POSITIVE-0.00014 HMM-Q01574-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-Q12455-FALSE_POSITIVE-3.8e-116 HMM-P25382-FALSE_POSITIVE-0.00016 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-P36130-FALSE_POSITIVE-0.00019 HMM-P38137-FALSE_POSITIVE-8.4e-10 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P07834-FALSE_POSITIVE-0.00028 HMM-P38137-FALSE_POSITIVE-8.4e-10 HMM-P38129-FALSE_POSITIVE-0.00045 HMM-P18851-FALSE_POSITIVE-0.00073

spermine SPERMIDINE-DEHYDROGENASE-RXN-reactionStatus=FALSE_NEGATIVE 4-aminobutanal uracil 3-hydroxypropionyl-CoA acrylate

RXN-6384-reactionStatus=TRUE_POSITIVE List of predictions: RXN-6421-reactionStatus=FALSE_NEGATIVE RXN-6421-reactionStatus=FALSE_NEGATIVE RXN-6423-reactionStatus=TRUE_NEGATIVE 1.3.1.2-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P28817-TRUE_POSITIVE-9.2163e-55 HMM-P28817-TRUE_POSITIVE-1.9e-68

1-(3-aminopropyl)-4-aminobutanal RXN-9015-reactionStatus=TRUE_NEGATIVE 1,3-diaminopropane 1-pyrroline dihydrouracil 3-hydroxypropionate

3-HYDROXYPROPIONATE-DEHYDROGENASE-RXN-reactionStatus=TRUE_NEGATIVE

MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P32771-FALSE_POSITIVE-3.01743e-85 BLAST-P38715-FALSE_POSITIVE-5.93767e-64 DIHYDROPYRIMIDINASE-RXN-reactionStatus=FALSE_NEGATIVE BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 List of predictions: BLAST-P14065-FALSE_POSITIVE-3.63052e-62 RXN-6424-reactionStatus=TRUE_NEGATIVE RXN-6381-reactionStatus=FALSE_NEGATIVE HMM-P32375-FALSE_POSITIVE-1.9e-08 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-Q12458-FALSE_POSITIVE-2.3e-81 HMM-P38715-FALSE_POSITIVE-7.3e-68 HMM-P38115-FALSE_POSITIVE-1.5e-53 HMM-Q04894-TRUE_POSITIVE-1.4e-49 HMM-P25377-TRUE_POSITIVE-1e-43 HMM-P47137-FALSE_POSITIVE-5.6e-23 HMM-P00331-FALSE_POSITIVE-3.1e-12 HMM-Q07551-FALSE_POSITIVE-3.4e-12 HMM-P00330-FALSE_POSITIVE-2.4e-11 HMM-P38113-FALSE_POSITIVE-3.9e-11 HMM-P07246-FALSE_POSITIVE-7.5e-11 HMM-Q07786-FALSE_POSITIVE-4.1e-10 HMM-P35497-FALSE_POSITIVE-4.3e-10 HMM-Q07993-FALSE_POSITIVE-6.1e-10 HMM-P32771-FALSE_POSITIVE-7.9e-09 HMM-P39713-FALSE_POSITIVE-1.6e-06 HMM-P39714-FALSE_POSITIVE-4.2e-06 HMM-Q6B208-FALSE_POSITIVE-4.4e-06

MARIBOES-1.1.1.276-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-Q05016-FALSE_POSITIVE-1.8e-45 HMM-P40580-FALSE_POSITIVE-4.4e-05 HMM-Q54AB5-FALSE_POSITIVE-4.4e-05 HMM-P40579-FALSE_POSITIVE-7.4e-05 HMM-P40471-FALSE_POSITIVE-0.00018 HMM-Q45U07-FALSE_POSITIVE-0.00019

1-(3-aminopropyl)-pyrrolinium 3-aminopropionaldehyde 3-ureidopropionate malonate semialdehyde L-aspartate

RXN-6382-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P40047-FALSE_POSITIVE-2.08365e-171 BLAST-P46367-TRUE_POSITIVE-6.98843e-170 BLAST-P32872-TRUE_POSITIVE-1.12781e-162 BLAST-P54115-TRUE_POSITIVE-2.54135e-148 BLAST-A9LRZ7-FALSE_POSITIVE-2.54135e-148 BLAST-P47771-FALSE_POSITIVE-2.21296e-136 BLAST-P54114-FALSE_POSITIVE-3.93669e-135 BLAST-P38694-FALSE_POSITIVE-3.41734e-108 MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE BLAST-P38067-FALSE_POSITIVE-1.01689e-84 List of predictions: List of predictions: BLAST-Q04458-FALSE_POSITIVE-9.19444e-70 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P22281-TRUE_POSITIVE-3.78136e-47 RXN-6425-reactionStatus=TRUE_NEGATIVE BETA-UREIDOPROPIONASE-RXN-reactionStatus=FALSE_NEGATIVE 2.6.1.18-RXN-reactionStatus=FALSE_NEGATIVE ASPDECARBOX-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-P46367-TRUE_POSITIVE-8.7e-285 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P40047-FALSE_POSITIVE-8.6e-282 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P32872-TRUE_POSITIVE-9.3e-245 HMM-P47771-FALSE_POSITIVE-1.5e-235 HMM-A9LRZ7-FALSE_POSITIVE-9.2e-235 HMM-P54115-TRUE_POSITIVE-9.2e-235 HMM-P54114-FALSE_POSITIVE-7.7e-232 HMM-P38067-FALSE_POSITIVE-2.5e-118 HMM-Q04458-FALSE_POSITIVE-4.4e-69 HMM-P38694-FALSE_POSITIVE-2.8e-32 HMM-P07275-FALSE_POSITIVE-1.3e-15 HMM-P22281-TRUE_POSITIVE-4.5e-15

1,5-diazabicyclononane β-alanine oxaloacetate

Pathway ID: Beta-Alanine-Biosynthesis-Saccharomyces cerevisiae 2-amino-3-carboxymuconate semialdehyde cyclohexane-1-carboxylate propylene L-ascorbate-6-phosphate

AMINO-CARBOXYMUCONATE-SEMIALDEHYDE-RXN-reactionStatus=FALSE_NEGATIVE R281-RXN-reactionStatus=TRUE_NEGATIVE 1.14.13.69-RXN-reactionStatus=TRUE_NEGATIVE RXN-8806-reactionStatus=TRUE_NEGATIVE RXN0-5214-reactionStatus=TRUE_NEGATIVE

2-aminomuconate semialdehyde cyclohexane-1-carboxyl-CoA (R)-1,2-epoxypropane (S)-1,2-epoxypropane 3-keto-L-gulonate 6-phosphate

RXN-8805-reactionStatus=TRUE_POSITIVE 4.2.99.19-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P25491-FALSE_POSITIVE-1.16698e-59 BLAST-P25491-FALSE_POSITIVE-1.16698e-59 HMM-P25491-FALSE_POSITIVE-9e-27 1.2.1.32-RXN-reactionStatus=TRUE_NEGATIVE R282-RXN-reactionStatus=TRUE_NEGATIVE HMM-P25491-FALSE_POSITIVE-9e-27 RXN0-705-reactionStatus=FALSE_NEGATIVE HMM-P39102-TRUE_POSITIVE-4.7e-14 HMM-P39102-TRUE_POSITIVE-7.2e-13 HMM-P53940-FALSE_POSITIVE-1.5e-06 HMM-P53940-FALSE_POSITIVE-1.8e-05 HMM-P25303-FALSE_POSITIVE-0.00055

2-amino-muconate AMINO-CARBOXYMUCONATE-SEMIALDEHYDE-RXN-reactionStatus=FALSE_NEGATIVE cyclohex-1-ene-1-carboxyl-CoA (R)-mevalonate 2-(R)-hydroxypropyl-CoM 2-(S)-hydroxypropyl-CoM L-xylulose-5-phosphate

3.5.99.5-RXN-reactionStatus=TRUE_POSITIVE List of predictions: HYDROXYMETHYLGLUTARYL-COA-REDUCTASE-RXN-reactionStatus=FALSE_NEGATIVE BLAST-Q00362-TRUE_POSITIVE-5.54588e-177 List of predictions: BLAST-P38903-TRUE_POSITIVE-1.17423e-150 HMM-P12683-FALSE_POSITIVE-1.5e-05 2-AMINOMUCONATE-REDUCTASE-RXN-reactionStatus=TRUE_NEGATIVE BLAST-P31383-TRUE_POSITIVE-8.2916e-146 1.1.1.268-RXN-reactionStatus=FALSE_NEGATIVE 1.1.1.269-RXN-reactionStatus=FALSE_NEGATIVE LXULRU5P-RXN-reactionStatus=FALSE_NEGATIVE HMM-P12684-FALSE_POSITIVE-0.00016 HMM-Q00362-TRUE_POSITIVE-4.2e-275 HMM-Q6B2D0-FALSE_POSITIVE-0.00016 HMM-P38903-TRUE_POSITIVE-9.5e-266 HMM-P31383-TRUE_POSITIVE-1.5e-232

α-ketoadipate 4-oxalocrotonate 3-hydroxy-3-methyl-glutaryl-CoA 2-oxopropyl-CoM L-ribulose-5-phosphate

MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P47176-TRUE_POSITIVE-1.49811e-110 2-KETO-ADIPATE-DEHYDROG-RXN-reactionStatus=TRUE_NEGATIVE BLAST-P38891-TRUE_POSITIVE-2.41111e-109 2-KETO-ADIPATE-DEHYDROG-RXN-reactionStatus=TRUE_NEGATIVE 4.1.1.77-RXN-reactionStatus=FALSE_NEGATIVE HYDROXYMETHYLGLUTARYL-COA-LYASE-RXN-reactionStatus=FALSE_NEGATIVE 1.8.1.5-RXN-reactionStatus=FALSE_NEGATIVE RIBULPEPIM-RXN-reactionStatus=FALSE_NEGATIVE HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P38891-TRUE_POSITIVE-7.5e-157

nitrilotriacetate glutaryl-CoA α-aminoadipate 2-oxopentenoate CO2 itaconate acetoacetate D-xylulose-5-phosphate

RXN-8988-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P53312-FALSE_POSITIVE-2.86841e-135 BLAST-P53598-FALSE_POSITIVE-2.05711e-95 RXN-9508-reactionStatus=TRUE_NEGATIVE GLUTARYL-COA-DEHYDROG-RXN-reactionStatus=TRUE_NEGATIVE HMM-P53312-FALSE_POSITIVE-1.5e-227 HMM-P53598-FALSE_POSITIVE-7.9e-170

RXN-8987-reactionStatus=TRUE_NEGATIVE

iminodiacetate RXN-9508-reactionStatus=TRUE_NEGATIVE glycolate glutaconyl-CoA itaconyl-CoA

RXN-9710-reactionStatus=TRUE_NEGATIVE RXN-9710-reactionStatus=TRUE_NEGATIVE GLYCOLATEDEHYDRO-RXN-reactionStatus=TRUE_NEGATIVE RXN-1744-reactionStatus=TRUE_NEGATIVE GLUTACONYL-COA-DECARBOXYLASE-RXN-reactionStatus=FALSE_NEGATIVE ITACONYL-COA-HYDRATASE-RXN-reactionStatus=TRUE_NEGATIVE

glycine glyoxylate succinate crotonyl-CoA L-citramalyl-CoA

MALSYN-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-B0KZR8-POSSIBLE_POSITIVE-0 BLAST-P30952-TRUE_POSITIVE-0 BLAST-B0KZS7-POSSIBLE_POSITIVE-0 BLAST-B0L026-POSSIBLE_POSITIVE-0 BLAST-P21826-TRUE_POSITIVE-0 BLAST-B0KZU5-POSSIBLE_POSITIVE-0 BLAST-B0KZY1-POSSIBLE_POSITIVE-0 BLAST-Q4KQC3-POSSIBLE_POSITIVE-4.10553e-101 BLAST-Q4KQC4-POSSIBLE_POSITIVE-1.44724e-100 GLYOCARBOLIG-RXN-reactionStatus=FALSE_NEGATIVE BLAST-Q4KQC8-POSSIBLE_POSITIVE-2.82118e-100 List of predictions: 3-HYDROXBUTYRYL-COA-DEHYDRATASE-RXN-reactionStatus=FALSE_NEGATIVE BLAST-Q4KQ91-POSSIBLE_POSITIVE-3.87373e-100 BLAST-P07342-FALSE_POSITIVE-1.94795e-69 List of predictions: BLAST-Q4KQ64-POSSIBLE_POSITIVE-6.44611e-99 MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE CITRAMALYL-COA-LYASE-RXN-reactionStatus=TRUE_NEGATIVE HMM-P07342-FALSE_POSITIVE-3e-40 HMM-P28817-FALSE_POSITIVE-2.7e-05 HMM-P30952-TRUE_POSITIVE-0 HMM-P39994-FALSE_POSITIVE-1.9e-05 HMM-B0KZR8-POSSIBLE_POSITIVE-0 HMM-B0KZS7-POSSIBLE_POSITIVE-0 HMM-B0L026-POSSIBLE_POSITIVE-0 HMM-B0KZU5-POSSIBLE_POSITIVE-0 HMM-B0KZY1-POSSIBLE_POSITIVE-0 HMM-P21826-TRUE_POSITIVE-0 HMM-Q4KQC3-POSSIBLE_POSITIVE-1e-45 HMM-Q4KQC4-POSSIBLE_POSITIVE-1.1e-45 HMM-Q4KQC8-POSSIBLE_POSITIVE-2.5e-45 HMM-Q4KQ91-POSSIBLE_POSITIVE-4.1e-45 HMM-Q4KQ64-POSSIBLE_POSITIVE-6.6e-43

tartronate semialdehyde succinyl-CoA β-ketoadipate 3-hydroxybutyryl-CoA pyruvate

MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P32771-FALSE_POSITIVE-3.01743e-85 BLAST-P38715-FALSE_POSITIVE-5.93767e-64 BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-Q12458-FALSE_POSITIVE-2.3e-81 RXN0-1134-reactionStatus=TRUE_POSITIVE HMM-P38715-FALSE_POSITIVE-7.3e-68 RXN-3641-reactionStatus=FALSE_NEGATIVE List of predictions: MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE HMM-P38115-FALSE_POSITIVE-1.5e-53 List of predictions: BLAST-P16387-TRUE_POSITIVE-0 BHBDCLOS-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: List of predictions: HMM-Q04894-TRUE_POSITIVE-1.4e-49 BLAST-P41338-FALSE_POSITIVE-3.26807e-59 BLAST-P32473-TRUE_POSITIVE-8.18423e-125 List of predictions: BLAST-P00175-TRUE_POSITIVE-5.46824e-166 BLAST-P00175-TRUE_POSITIVE-5.46824e-166 malate HMM-P25377-TRUE_POSITIVE-1e-43 RXN0-5289-reactionStatus=FALSE_NEGATIVE RXN-1744-reactionStatus=TRUE_NEGATIVE 3-OXOADIPATE-COA-TRANSFERASE-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P27796-FALSE_POSITIVE-4.52626e-58 3-OXOADIPATE-COA-TRANSFERASE-RXN-reactionStatus=FALSE_NEGATIVE HMM-P16387-TRUE_POSITIVE-2.1e-244 CITRAMALYL-COA-LYASE-RXN-reactionStatus=TRUE_NEGATIVE BLAST-Q02207-FALSE_POSITIVE-1.70589e-84 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-P47137-FALSE_POSITIVE-5.6e-23 HMM-P41338-FALSE_POSITIVE-7.2e-88 HMM-P32473-TRUE_POSITIVE-1.4e-230 HMM-Q07540-FALSE_POSITIVE-1.3e-09 HMM-Q07540-FALSE_POSITIVE-1.3e-09 HMM-Q07551-FALSE_POSITIVE-9.9e-14 HMM-P27796-FALSE_POSITIVE-7.1e-76 HMM-P19262-FALSE_POSITIVE-2e-07 HMM-P00331-FALSE_POSITIVE-9.2e-13 HMM-P12695-FALSE_POSITIVE-9e-07 HMM-P00330-FALSE_POSITIVE-7.5e-12 HMM-P38113-FALSE_POSITIVE-1.3e-11 HMM-P07246-FALSE_POSITIVE-2.5e-11 HMM-Q07786-FALSE_POSITIVE-1.2e-09 HMM-P35497-FALSE_POSITIVE-1.2e-09 HMM-Q07993-FALSE_POSITIVE-1.7e-09 HMM-P32771-FALSE_POSITIVE-2e-08 HMM-P39713-FALSE_POSITIVE-7.6e-07 HMM-P39714-FALSE_POSITIVE-4.3e-06 HMM-Q6B208-FALSE_POSITIVE-5e-06

MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P32473-FALSE_POSITIVE-2.33193e-65 D-glycerate β-ketoadipyl-CoA acetoacetyl-CoA L-lactate Pyruvate-dehydrogenase-acetylDHlipoyl HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P16387-FALSE_POSITIVE-6.1e-12

RXN-3641-reactionStatus=FALSE_NEGATIVE ACETYL-COA-ACETYLTRANSFER-RXN-reactionStatus=TRUE_POSITIVE RXN0-1133-reactionStatus=TRUE_POSITIVE RXN0-1133-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.1.4-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: List of predictions: List of predictions: List of predictions: List of predictions: BLAST-P41338-FALSE_POSITIVE-3.26807e-59 BLAST-P41338-TRUE_POSITIVE-0 HMM-P12695-TRUE_POSITIVE-6.1e-165 HMM-P12695-TRUE_POSITIVE-6.1e-165 GLY3KIN-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P25337-FALSE_POSITIVE-3.96292e-40 BLAST-P27796-FALSE_POSITIVE-4.52626e-58 BLAST-P27796-FALSE_POSITIVE-9.02747e-61 HMM-P19262-FALSE_POSITIVE-1.6e-89 HMM-P19262-FALSE_POSITIVE-1.6e-89 HMM-P25337-FALSE_POSITIVE-6e-57 HMM-P41338-FALSE_POSITIVE-7.2e-88 HMM-P41338-TRUE_POSITIVE-1e-266 HMM-P16451-FALSE_POSITIVE-9.6e-07 HMM-P16451-FALSE_POSITIVE-9.6e-07 HMM-P27796-FALSE_POSITIVE-7.1e-76 HMM-P27796-FALSE_POSITIVE-1.5e-89 HMM-Q6B1U7-FALSE_POSITIVE-9.6e-07 HMM-Q6B1U7-FALSE_POSITIVE-9.6e-07

RXN0-1134-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P16387-TRUE_POSITIVE-0 BLAST-P32473-TRUE_POSITIVE-8.18423e-125 3-phosphoglycerate hydroxypyruvate acetyl-CoA citrate HMM-P16387-TRUE_POSITIVE-2.1e-244 Pyruvate-dehydrogenase-dihydrolipoate HMM-P32473-TRUE_POSITIVE-1.4e-230 HMM-P19262-FALSE_POSITIVE-2e-07 HMM-P12695-FALSE_POSITIVE-9e-07

ACETATE--COA-LIGASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE HMM-P52910-TRUE_POSITIVE-0 RXN0-1132-reactionStatus=TRUE_POSITIVE HMM-Q01574-TRUE_POSITIVE-0 List of predictions: MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE HMM-Q66RJ0-FALSE_POSITIVE-0 BLAST-P09624-TRUE_POSITIVE-4.38686e-176 List of predictions: HMM-P38137-FALSE_POSITIVE-6e-06 BLAST-Q02733-FALSE_POSITIVE-1.95829e-80 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-P41921-FALSE_POSITIVE-2.19532e-49 BLAST-P52910-TRUE_POSITIVE-0 HMM-P09624-TRUE_POSITIVE-1.2e-267 MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE CITTRANS-RXN-reactionStatus=FALSE_NEGATIVE BLAST-Q01574-TRUE_POSITIVE-0 HMM-Q02733-FALSE_POSITIVE-2.2e-73 HMM-P52910-TRUE_POSITIVE-0 MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE HMM-P41921-FALSE_POSITIVE-1.6e-35 HMM-Q01574-TRUE_POSITIVE-0 List of predictions: HMM-P29509-FALSE_POSITIVE-2.3e-06 HMM-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 HMM-P38816-FALSE_POSITIVE-0.00012 HMM-P38137-FALSE_POSITIVE-9.8e-11 BLAST-P52910-TRUE_POSITIVE-0 HMM-P40215-FALSE_POSITIVE-0.00015 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-9.8e-11

MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P00175-TRUE_POSITIVE-5.46824e-166 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-Q07540-FALSE_POSITIVE-1.3e-09

CITRATE-PRO-3S-LYASE-THIOLESTERASE-RXN-reactionStatus=TRUE_NEGATIVE CITC-RXN-reactionStatus=FALSE_NEGATIVE CITTRANS-RXN-reactionStatus=FALSE_NEGATIVE CITTRANS-RXN-reactionStatus=FALSE_NEGATIVE CITTRANS-RXN-reactionStatus=FALSE_NEGATIVE

CITRATE-LYASE

2.3.1.49-RXN-reactionStatus=TRUE_NEGATIVE CITRATE-PRO-3S-LYASE-THIOLESTERASE-RXN-reactionStatus=TRUE_NEGATIVE CITRYLY-RXN-reactionStatus=FALSE_NEGATIVE CITTRANS-RXN-reactionStatus=FALSE_NEGATIVE CITRYLY-RXN-reactionStatus=FALSE_NEGATIVE CITTRANS-RXN-reactionStatus=FALSE_NEGATIVE CITC-RXN-reactionStatus=FALSE_NEGATIVE

DEACETYL-CITRATE-LYASE CITRYL-ACP Citrate-Lyase-Citryl-Forms

CITRYLY-RXN-reactionStatus=FALSE_NEGATIVE CITRYLY-RXN-reactionStatus=FALSE_NEGATIVE

oxaloacetate

MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P38891-TRUE_POSITIVE-7.5e-157

L-aspartate

Pathway ID: CARBOXYLATES-DEG-Saccharomyces cerevisiae D-erythrose-4-phosphate

DAHPSYN-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P14843-TRUE_POSITIVE-3.59341e-140 BLAST-P32449-TRUE_POSITIVE-5.98853e-130 HMM-P32449-TRUE_POSITIVE-9e-246 HMM-P14843-TRUE_POSITIVE-1.1e-236

3-deoxy-D-arabino-heptulosonate-7-phosphate

3-DEHYDROQUINATE-SYNTHASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P08566-TRUE_POSITIVE-0 HMM-P08566-TRUE_POSITIVE-0

3-dehydroquinate

3-DEHYDROQUINATE-DEHYDRATASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P08566-TRUE_POSITIVE-0 HMM-P08566-TRUE_POSITIVE-0

3-dehydro-shikimate

RXN-7968-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-P08566-FALSE_POSITIVE-4.1e-07

SHIKIMATE-5-DEHYDROGENASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P08566-TRUE_POSITIVE-0 HMM-P08566-TRUE_POSITIVE-0

shikimate

SHIKIMATE-KINASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P08566-TRUE_POSITIVE-0 HMM-P08566-TRUE_POSITIVE-0

shikimate-3-phosphate

2.5.1.19-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P08566-TRUE_POSITIVE-0 HMM-P08566-TRUE_POSITIVE-0

5-enolpyruvyl-shikimate-3-phosphate

CHORISMATE-SYNTHASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P28777-TRUE_POSITIVE-2.92091e-144 HMM-P28777-TRUE_POSITIVE-1.3e-223

chorismate

Pathway ID: Chorismate-Biosynthesis-Saccharomyces cerevisiae pantothenate

PANTOTHENATE-KIN-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-Q04430-TRUE_POSITIVE-7.53246e-55 HMM-Q04430-TRUE_POSITIVE-1.9e-14

D-4'-phosphopantothenate

P-PANTOCYSLIG-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-P36076-FALSE_POSITIVE-1.4e-06

R-4'-phosphopantothenoyl-L-cysteine

P-PANTOCYSDECARB-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-P36076-FALSE_POSITIVE-3.2e-49 HMM-P36024-FALSE_POSITIVE-5.2e-30 HMM-Q08438-FALSE_POSITIVE-5.6e-21

4'-phosphopantetheine

PANTEPADENYLYLTRAN-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-P53332-FALSE_POSITIVE-5.2e-26

dephospho-CoA

DEPHOSPHOCOAKIN-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-Q03941-FALSE_POSITIVE-8.8e-69

coenzyme A

Pathway ID: CoA-Biosynthesis-Saccharomyces cerevisiae L-serine

MARIBOES-1.1.1.276-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-Q05016-FALSE_POSITIVE-1.8e-45 HMM-P40580-FALSE_POSITIVE-3.4e-06 HMM-Q54AB5-FALSE_POSITIVE-3.4e-06 HMM-P40579-FALSE_POSITIVE-6.3e-06 HMM-P40471-FALSE_POSITIVE-1.8e-05 HMM-Q45U07-FALSE_POSITIVE-1.8e-05 HMM-P38286-FALSE_POSITIVE-0.00053

hydrogen sulfide 2-aminomalonate-semialdehyde O-acetyl-L-serine cystathionine

ACSERLY-RXN-reactionStatus=TRUE_POSITIVE ACSERLY-RXN-reactionStatus=TRUE_POSITIVE CYSTAGLY-RXN-reactionStatus=TRUE_POSITIVE CYSTATHIONINE-BETA-LYASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: List of predictions: List of predictions: BLAST-P06106-TRUE_POSITIVE-0 BLAST-P06106-TRUE_POSITIVE-0 BLAST-P31373-TRUE_POSITIVE-1.999e-101 BLAST-P31373-FALSE_POSITIVE-1.07861e-92 BLAST-P53206-TRUE_POSITIVE-9.22125e-97 BLAST-P53206-TRUE_POSITIVE-9.22125e-97 BLAST-P53101-FALSE_POSITIVE-2.11097e-54 CYSTATHIONINE-BETA-SYNTHASE-RXN-reactionStatus=TRUE_POSITIVE BLAST-P43623-TRUE_POSITIVE-1.74937e-86 BLAST-P32582-FALSE_POSITIVE-1.71288e-48 BLAST-P32582-FALSE_POSITIVE-1.71288e-48 BLAST-P43623-FALSE_POSITIVE-1.73391e-42 List of predictions: BLAST-P53101-TRUE_POSITIVE-1.96993e-68 BLAST-O94073-FALSE_POSITIVE-1.19684e-47 BLAST-O94073-FALSE_POSITIVE-1.19684e-47 HMM-P31373-TRUE_POSITIVE-1.6e-150 BLAST-P32582-TRUE_POSITIVE-6.87031e-108 HMM-P31373-FALSE_POSITIVE-7.4e-116 HMM-P53206-TRUE_POSITIVE-2e-112 HMM-P53206-TRUE_POSITIVE-2e-112 HMM-P53101-FALSE_POSITIVE-4.3e-38 BLAST-O94073-POSSIBLE_POSITIVE-1.26365e-106 HMM-P43623-TRUE_POSITIVE-1.1e-104 HMM-P32582-FALSE_POSITIVE-2.8e-111 HMM-P32582-FALSE_POSITIVE-2.8e-111 HMM-P06106-FALSE_POSITIVE-7e-35 HMM-P32582-TRUE_POSITIVE-1.1e-97 HMM-P53101-TRUE_POSITIVE-9.3e-62 HMM-O94073-FALSE_POSITIVE-3.8e-108 HMM-O94073-FALSE_POSITIVE-3.8e-108 HMM-P43623-FALSE_POSITIVE-4e-15 HMM-O94073-POSSIBLE_POSITIVE-2.9e-95 HMM-P06106-FALSE_POSITIVE-1.3e-52 HMM-P00927-FALSE_POSITIVE-4.1e-06 HMM-P00927-FALSE_POSITIVE-4.1e-06 HMM-P38716-FALSE_POSITIVE-7e-15 HMM-P53206-FALSE_POSITIVE-0.00015 HMM-P38716-FALSE_POSITIVE-3.2e-25 HMM-P36007-FALSE_POSITIVE-1.2e-05 HMM-P36007-FALSE_POSITIVE-1.2e-05 HMM-Q12198-FALSE_POSITIVE-8.4e-05 HMM-Q12198-FALSE_POSITIVE-1.6e-05 HMM-P17324-FALSE_POSITIVE-0.0004 HMM-P17324-FALSE_POSITIVE-0.0004 HMM-P47164-FALSE_POSITIVE-0.0002 HMM-P47164-FALSE_POSITIVE-5.1e-05 HMM-P25379-FALSE_POSITIVE-0.00048 HMM-P25379-FALSE_POSITIVE-0.00048 HMM-Q04533-FALSE_POSITIVE-0.00073

L-cysteine L-homocysteine

MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE

N-acetyl-L-cysteine

Pathway ID: CYSTEINE-SYN-Saccharomyces cerevisiae formaldehyde 6-phospho-D-gluconate

MARIBOES-3.1.3.1-RXN-reactionStatus=TRUE_POSITIVE RXN-3341-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P11491-TRUE_POSITIVE-4.33135e-102 BLAST-P38720-TRUE_POSITIVE-0 RXN-6581-reactionStatus=TRUE_NEGATIVE RXN-2961-reactionStatus=FALSE_NEGATIVERXN-2882-reactionStatus=TRUE_NEGATIVE RXN-2881-reactionStatus=TRUE_NEGATIVE BLAST-Q66RD0-FALSE_POSITIVE-1.28731e-49 BLAST-P53319-TRUE_POSITIVE-0 HMM-P11491-TRUE_POSITIVE-8.1e-29 HMM-P38720-TRUE_POSITIVE-0 HMM-Q66RD0-FALSE_POSITIVE-1.8e-28 HMM-P53319-TRUE_POSITIVE-0

S-hydroxymethylmycothiol 5,10-methylene-tetrahydromethanopterin 5,10-methylene-THF D-gluconate D-ribulose-5-phosphate

METHYLENETHFDEHYDROG-NADP-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P07245-TRUE_POSITIVE-0 BLAST-P09440-TRUE_POSITIVE-0 1.2.1.66-RXN-reactionStatus=FALSE_NEGATIVE S-hydroxymethylglutathione RXN-2883-reactionStatus=TRUE_NEGATIVE R10-RXN-reactionStatus=FALSE_NEGATIVE HMM-P07245-TRUE_POSITIVE-0 HMM-P09440-TRUE_POSITIVE-0 HMM-Q02046-FALSE_POSITIVE-1e-11

RXN-2962-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P32771-TRUE_POSITIVE-6.77856e-153 HMM-P32771-TRUE_POSITIVE-2.2e-202 HMM-P38113-FALSE_POSITIVE-1.3e-09 HMM-P07246-FALSE_POSITIVE-6.7e-09 HMM-P00330-FALSE_POSITIVE-1.5e-08 HMM-Q07993-FALSE_POSITIVE-2.8e-08 5,10-methenyltetrahydromethanopterin 5,10-methenyltetrahydrofolate FORMALDEHYDE-DEHYDROGENASE-RXN-reactionStatus=FALSE_NEGATIVE hexulose 6-phosphate HMM-P00331-FALSE_POSITIVE-4.1e-08 HMM-P35497-FALSE_POSITIVE-2e-07 HMM-Q07786-FALSE_POSITIVE-2.4e-07 HMM-P39713-FALSE_POSITIVE-2.2e-05 HMM-P39714-FALSE_POSITIVE-6.3e-05 HMM-Q6B208-FALSE_POSITIVE-6.6e-05 HMM-Q04894-FALSE_POSITIVE-0.00024

6PGLUCONOLACT-RXN-reactionStatus=TRUE_POSITIVE List of predictions: METHENYLTHFCYCLOHYDRO-RXN-reactionStatus=TRUE_POSITIVE BLAST-Q6B1T2-FALSE_POSITIVE-1.34545e-55 List of predictions: BLAST-P50278-TRUE_POSITIVE-4.91462e-53 BLAST-P07245-TRUE_POSITIVE-0 BLAST-P11412-FALSE_POSITIVE-2.28096e-49 BLAST-P09440-TRUE_POSITIVE-0 BLAST-P37262-TRUE_POSITIVE-3.05806e-49 S-formylmycothiol S-formylglutathione 3.5.4.27-RXN-reactionStatus=FALSE_NEGATIVE R12-RXN-reactionStatus=FALSE_NEGATIVE HMM-P07245-TRUE_POSITIVE-0 BLAST-P38858-TRUE_POSITIVE-2.63542e-44 HMM-P09440-TRUE_POSITIVE-0 HMM-P38858-TRUE_POSITIVE-1.4e-52 HMM-Q02046-FALSE_POSITIVE-8.2e-11 HMM-P50278-TRUE_POSITIVE-1.2e-48 HMM-P53315-TRUE_POSITIVE-7.6e-47 HMM-P37262-TRUE_POSITIVE-1.5e-42

S-FORMYLGLUTATHIONE-HYDROLASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P33339-FALSE_POSITIVE-7.67177e-78 RXN1G-129-reactionStatus=TRUE_NEGATIVE 5-formyl-tetrahydromethanopterin 10-formyl-tetrahydrofolate D-fructose-6-phosphate BLAST-P40363-TRUE_POSITIVE-4.90373e-64 HMM-P40363-TRUE_POSITIVE-1.8e-75

FORMATETHFLIG-RXN-reactionStatus=TRUE_POSITIVE List of predictions: PGLUCISOM-RXN-reactionStatus=TRUE_POSITIVE BLAST-P09440-TRUE_POSITIVE-0 List of predictions: RXN-2884-reactionStatus=TRUE_NEGATIVE BLAST-P07245-TRUE_POSITIVE-0 BLAST-P12709-TRUE_POSITIVE-0 HMM-P09440-TRUE_POSITIVE-0 HMM-P12709-TRUE_POSITIVE-0 HMM-P07245-TRUE_POSITIVE-0

formate β-D-glucose-6-phosphate

GLU6PDEHYDROG-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-Q6B1T2-POSSIBLE_POSITIVE-0 BLAST-P11412-TRUE_POSITIVE-0 HMM-P11412-TRUE_POSITIVE-5.6e-278 HMM-Q6B1T2-POSSIBLE_POSITIVE-3e-277

D-glucono-δ-lactone-6-phosphate

Pathway ID: Formaldehyde-Oxidation-Saccharomyces cerevisiae all-trans-farnesyl diphosphate

FARNESYLTRANSTRANSFERASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-Q12051-TRUE_POSITIVE-1.75076e-66 HMM-Q12051-TRUE_POSITIVE-5.5e-61 HMM-P18900-FALSE_POSITIVE-1.9e-08 HMM-P08524-FALSE_POSITIVE-5.7e-06

all-trans-geranyl-geranyl diphosphate

Pathway ID: GGPP-Biosynthesis-Saccharomyces cerevisiae L-glutamate

GLUTAMATE-DEHYDROGENASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P33327-TRUE_POSITIVE-0 BLAST-P07262-FALSE_POSITIVE-1.05556e-110 BLAST-P39708-FALSE_POSITIVE-1.80156e-108 GABATRANSAM-RXN-reactionStatus=TRUE_POSITIVE BLAST-P39703-FALSE_POSITIVE-7.50934e-61 List of predictions: HMM-P07262-FALSE_POSITIVE-1e-151 BLAST-A5H0J7-FALSE_POSITIVE-1.11779e-149 ASPAMINOTRANS-RXN-reactionStatus=TRUE_POSITIVE HMM-P39708-FALSE_POSITIVE-8.7e-149 BLAST-P17649-TRUE_POSITIVE-5.45571e-149 List of predictions: BLAST-P07991-FALSE_POSITIVE-1.80061e-49 BLAST-P23542-TRUE_POSITIVE-1.11445e-106 MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE BLAST-P18544-FALSE_POSITIVE-2.05957e-46 GLUTDECARBOX-RXN-reactionStatus=TRUE_POSITIVE BLAST-Q01802-TRUE_POSITIVE-1.34166e-73 GLUTAMATE-DEHYDROGENASE-NADP+-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-A5H0J7-FALSE_POSITIVE-3.3e-114 List of predictions: HMM-P23542-TRUE_POSITIVE-5.7e-143 List of predictions: BLAST-P47176-TRUE_POSITIVE-1.49811e-110 HMM-P17649-TRUE_POSITIVE-4.9e-113 BLAST-Q04792-TRUE_POSITIVE-1.78495e-94 HMM-Q01802-TRUE_POSITIVE-7.1e-74 MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE METHYLASPARTATE-MUTASE-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P07262-FALSE_POSITIVE-8.66749e-119 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-P18544-FALSE_POSITIVE-8.5e-23 HMM-Q04792-TRUE_POSITIVE-6.7e-134 HMM-P47039-FALSE_POSITIVE-2e-32 BLAST-P39708-FALSE_POSITIVE-1.27301e-116 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P07991-FALSE_POSITIVE-7.3e-17 HMM-Q05567-FALSE_POSITIVE-1.4e-09 HMM-P52892-FALSE_POSITIVE-4.3e-10 HMM-P07262-FALSE_POSITIVE-8e-122 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-Q5DWF2-FALSE_POSITIVE-2.9e-09 HMM-Q66RF8-FALSE_POSITIVE-7.7e-10 HMM-P39708-FALSE_POSITIVE-1.3e-118 HMM-Q5DWF5-FALSE_POSITIVE-3.1e-09 HMM-P52893-FALSE_POSITIVE-2.3e-09 HMM-Q4R1J2-FALSE_POSITIVE-9.2e-09 HMM-Q4R1J1-FALSE_POSITIVE-3.4e-07 MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE HMM-Q66R22-FALSE_POSITIVE-3.6e-07 List of predictions: HMM-P50277-FALSE_POSITIVE-3.6e-07 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P38891-TRUE_POSITIVE-7.5e-157

L-aspartate N-acetyl-L-glutamate (2S, 3S)-3-methylaspartate 2-oxoglutarate 4-aminobutyrate

GABATRANSAM-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-A5H0J7-FALSE_POSITIVE-1.11779e-149 BLAST-P17649-TRUE_POSITIVE-5.45571e-149 BLAST-P07991-FALSE_POSITIVE-1.80061e-49 BLAST-P18544-FALSE_POSITIVE-2.05957e-46 HMM-A5H0J7-FALSE_POSITIVE-3.3e-114 HMM-P17649-TRUE_POSITIVE-4.9e-113 HMM-P18544-FALSE_POSITIVE-8.5e-23 HMM-P07991-FALSE_POSITIVE-7.3e-17 MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE HMM-Q5DWF2-FALSE_POSITIVE-2.9e-09 List of predictions: List of predictions: ASPARTASE-RXN-reactionStatus=FALSE_NEGATIVE HMM-Q5DWF5-FALSE_POSITIVE-3.1e-09 KETOGLUTREDUCT-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 List of predictions: HMM-Q4R1J2-FALSE_POSITIVE-9.2e-09 List of predictions: BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P08417-FALSE_POSITIVE-2.73079e-101 METHYLASPARTATE-AMMONIA-LYASE-RXN-reactionStatus=FALSE_NEGATIVE HMM-Q4R1J1-FALSE_POSITIVE-3.4e-07 BLAST-P40961-FALSE_POSITIVE-3.29006e-80 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P08417-FALSE_POSITIVE-8.1e-108 HMM-Q66R22-FALSE_POSITIVE-3.6e-07 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P50277-FALSE_POSITIVE-3.6e-07

RXN-6902-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-A5H0J7-FALSE_POSITIVE-1.11779e-149 BLAST-P17649-TRUE_POSITIVE-5.45571e-149 BLAST-P07991-FALSE_POSITIVE-2.97955e-48 HMM-A5H0J7-FALSE_POSITIVE-1.2e-240 HMM-P17649-TRUE_POSITIVE-3.3e-239 HMM-P18544-FALSE_POSITIVE-2.1e-13 HMM-P07991-FALSE_POSITIVE-9.5e-11

oxaloacetate fumarate mesaconate (R)-2-hydroxyglutarate succinate semialdehyde

RXN-6903-reactionStatus=TRUE_POSITIVE SUCCINATE-SEMIALDEHYDE-DEHYDROGENASE-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: List of predictions: BLAST-P38067-TRUE_POSITIVE-2.1398e-148 BLAST-P38067-FALSE_POSITIVE-4.47258e-121 BLAST-P40047-FALSE_POSITIVE-1.21204e-94 BLAST-P40047-FALSE_POSITIVE-1.76554e-75 BLAST-P46367-FALSE_POSITIVE-4.32337e-82 BLAST-P46367-FALSE_POSITIVE-2.32721e-72 BLAST-P47771-FALSE_POSITIVE-1.31226e-79 BLAST-P54115-FALSE_POSITIVE-1.10018e-66 BLAST-P54114-FALSE_POSITIVE-1.84752e-79 BLAST-A9LRZ7-FALSE_POSITIVE-1.10018e-66 BLAST-P54115-FALSE_POSITIVE-8.5132e-76 BLAST-P32872-FALSE_POSITIVE-9.79171e-66 BLAST-A9LRZ7-FALSE_POSITIVE-8.5132e-76 BLAST-P47771-FALSE_POSITIVE-4.62765e-61 BLAST-P32872-FALSE_POSITIVE-4.37225e-72 BLAST-P54114-FALSE_POSITIVE-6.19888e-60 BLAST-P38694-FALSE_POSITIVE-1.10263e-59 BLAST-P38694-FALSE_POSITIVE-4.23899e-47 HMM-P38067-TRUE_POSITIVE-3.1e-213 HMM-P38067-FALSE_POSITIVE-6.1e-151 S-2-METHYLMALATE-DEHYDRATASE-RXN-reactionStatus=TRUE_NEGATIVE RXN-1082-reactionStatus=FALSE_NEGATIVE HMM-P40047-FALSE_POSITIVE-3.8e-125 HMM-P40047-FALSE_POSITIVE-1.7e-77 HMM-P46367-FALSE_POSITIVE-6e-103 HMM-P46367-FALSE_POSITIVE-7.7e-67 HMM-P54114-FALSE_POSITIVE-2.1e-95 HMM-A9LRZ7-FALSE_POSITIVE-4.5e-48 HMM-P47771-FALSE_POSITIVE-4.4e-95 HMM-P54115-FALSE_POSITIVE-4.5e-48 HMM-P54115-FALSE_POSITIVE-1.1e-83 HMM-P32872-FALSE_POSITIVE-2.9e-42 HMM-A9LRZ7-FALSE_POSITIVE-1.1e-83 HMM-P47771-FALSE_POSITIVE-1.9e-37 HMM-P32872-FALSE_POSITIVE-8.7e-77 HMM-P54114-FALSE_POSITIVE-1.7e-36 HMM-P38694-FALSE_POSITIVE-6.7e-33 HMM-P38694-FALSE_POSITIVE-3.5e-17 HMM-P07275-FALSE_POSITIVE-7.5e-15 HMM-Q04458-FALSE_POSITIVE-3.7e-09 HMM-Q04458-FALSE_POSITIVE-2.9e-13 HMM-P07275-FALSE_POSITIVE-5.3e-09 HMM-P22281-FALSE_POSITIVE-2.6e-08 HMM-P22281-FALSE_POSITIVE-1e-05

(S)-citramalate (R)-2-hydroxyglutaryl-CoA 4-hydroxybutyrate succinate

CITRAMALATE-LYASE-RXN-reactionStatus=FALSE_NEGATIVE RXN-1083-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE

pyruvate glutaconyl-CoA succinyl-CoA

MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: List of predictions: BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P00175-TRUE_POSITIVE-5.46824e-166 BLAST-P00175-TRUE_POSITIVE-5.46824e-166 CITRAMALATE-LYASE-RXN-reactionStatus=FALSE_NEGATIVE GLUTACONYL-COA-DECARBOXYLASE-RXN-reactionStatus=FALSE_NEGATIVE HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-P16387-FALSE_POSITIVE-3.8e-12 HMM-Q07540-FALSE_POSITIVE-1.3e-08 HMM-Q07540-FALSE_POSITIVE-1.3e-08

acetyl-CoA L-lactate crotonyl-CoA

MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE

MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 R22-RXN-reactionStatus=FALSE_NEGATIVE BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-1.8e-10 HMM-P38137-FALSE_POSITIVE-1.8e-10

acetate butyryl-CoA

R11-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: List of predictions: List of predictions: BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P32473-FALSE_POSITIVE-1.1e-55 BLAST-P52910-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P16387-FALSE_POSITIVE-3.8e-12 HMM-P16387-FALSE_POSITIVE-3.8e-12 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-1.8e-10 HMM-P38137-FALSE_POSITIVE-1.8e-10

2-ketopentanoate butyrate

Pathway ID: GLUTAMATE-DEG-Saccharomyces cerevisiae L-glutamine

GLUTAMATE-SYNTHASE-NADH-RXN-reactionStatus=FALSE_NEGATIVE

GLUTAMATESYN-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-Q12680-TRUE_POSITIVE-0 HMM-Q12680-TRUE_POSITIVE-0

GLUTAMATE-SYNTHASE-FERREDOXIN-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-Q12680-FALSE_POSITIVE-0 HMM-Q12680-FALSE_POSITIVE-0

L-glutamate

GLUTAMATE-DEHYDROGENASE-NADP+-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P07262-FALSE_POSITIVE-8.66749e-119 BLAST-P39708-FALSE_POSITIVE-1.27301e-116 HMM-P07262-FALSE_POSITIVE-8e-122 HMM-P39708-FALSE_POSITIVE-1.3e-118

GLUTDEHYD-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P39708-TRUE_POSITIVE-0 MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE BLAST-P07262-TRUE_POSITIVE-0 List of predictions: HMM-P07262-TRUE_POSITIVE-0 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 HMM-P39708-TRUE_POSITIVE-0 MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P38891-TRUE_POSITIVE-7.5e-157 GLUTAMATE-SYNTHASE-FERREDOXIN-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-Q12680-FALSE_POSITIVE-0 HMM-Q12680-FALSE_POSITIVE-0

MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P38891-TRUE_POSITIVE-7.5e-157

N-acetyl-L-glutamate 2-oxoglutarate

Pathway ID: GLUTAMATE-SYN-Saccharomyces cerevisiae L-glutamate

MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: GLUTAMINESYN-RXN-reactionStatus=TRUE_POSITIVE BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 List of predictions: BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE BLAST-P32288-TRUE_POSITIVE-0 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P32288-TRUE_POSITIVE-6.2e-264 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P38891-TRUE_POSITIVE-7.5e-157

2-oxoglutarate N-acetyl-L-glutamate L-glutamine

Pathway ID: GLUTAMINE-SYN-Saccharomyces cerevisiae L-arginine glycine DIHYDROLIPOYL-GCVH

RXN-8629-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P09624-TRUE_POSITIVE-4.38686e-176 BLAST-Q02733-FALSE_POSITIVE-1.95829e-80 BLAST-P41921-FALSE_POSITIVE-4.03551e-50 GLYCINE-AMIDINOTRANSFERASE-RXN-reactionStatus=FALSE_NEGATIVE GLYCINE-AMIDINOTRANSFERASE-RXN-reactionStatus=FALSE_NEGATIVE HMM-P09624-TRUE_POSITIVE-6.4e-278 HMM-Q02733-FALSE_POSITIVE-3e-75 HMM-P41921-FALSE_POSITIVE-8.9e-39 HMM-P29509-FALSE_POSITIVE-6.3e-05

GCVT-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P49095-TRUE_POSITIVE-0 guanidinoacetate PROTEIN-LIPOYLLYSINE BLAST-P48015-TRUE_POSITIVE-7.71973e-92 HMM-P49095-TRUE_POSITIVE-0 HMM-P48015-TRUE_POSITIVE-7.4e-137

GCVP-RXN-reactionStatus=TRUE_POSITIVE List of predictions: GUANIDINOACETATE-N-METHYLTRANSFERASE-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P49095-TRUE_POSITIVE-0 HMM-P49095-TRUE_POSITIVE-0

creatine AMINOMETHYLDIHYDROLIPOYL-GCVH

Pathway ID: GLYCINE-DEG-Saccharomyces cerevisiae ammonia CO2 L-threonine L-serine

MARIBOES-1.1.1.276-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-Q05016-FALSE_POSITIVE-1.8e-45 HMM-P40580-FALSE_POSITIVE-1.1e-07 HMM-Q54AB5-FALSE_POSITIVE-1.1e-07 HMM-P40579-FALSE_POSITIVE-2.3e-07 HMM-P40471-FALSE_POSITIVE-8.1e-07 HMM-Q45U07-FALSE_POSITIVE-8.5e-07 HMM-P38286-FALSE_POSITIVE-4.6e-05 HMM-P32573-FALSE_POSITIVE-9.1e-05 HMM-Q02207-FALSE_POSITIVE-0.00019 HMM-Q07530-FALSE_POSITIVE-0.00079

glycine 2-aminomalonate-semialdehyde

Pathway ID: GLYCINE-SYN-Saccharomyces cerevisiae uroporphyrinogen-III

UROGENDECARBOX-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P32347-TRUE_POSITIVE-2.70247e-103 HMM-P32347-TRUE_POSITIVE-5.6e-145

coproporphyrinogen III

RXN0-1461-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P11353-TRUE_POSITIVE-1.1648e-90 HMM-P11353-TRUE_POSITIVE-4.9e-126

HEMN-RXN-reactionStatus=FALSE_NEGATIVE

protoporphyrinogen IX

PROTOPORGENOXI-RXN-reactionStatus=TRUE_POSITIVE List of predictions: HMM-P40012-TRUE_POSITIVE-2.8e-13

protoporphyrin IX

PROTOHEMEFERROCHELAT-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P16622-TRUE_POSITIVE-9.86461e-100 HMM-P16622-TRUE_POSITIVE-6.7e-21

protoheme IX

Pathway ID: HEME-SYN-Saccharomyces cerevisiae 5-phosphoribosyl 1-pyrophosphate

ATPPHOSPHORIBOSYLTRANS-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P00498-TRUE_POSITIVE-1.6704e-140 HMM-P00498-TRUE_POSITIVE-6.3e-193

phosphoribosyl-ATP

HISTPRATPHYD-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P00815-TRUE_POSITIVE-0 HMM-P00815-TRUE_POSITIVE-0

phosphoribosyl-AMP

HISTCYCLOHYD-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P00815-TRUE_POSITIVE-0 HMM-P00815-TRUE_POSITIVE-0

phosphoribosylformiminoAICAR-phosphate

PRIBFAICARPISOM-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P40545-TRUE_POSITIVE-3.61503e-103 HMM-P40545-TRUE_POSITIVE-5.2e-184 HMM-P33734-FALSE_POSITIVE-0.00042

phosphoribulosylformimino-AICAR-P

GLUTAMIDOTRANS-RXN-reactionStatus=TRUE_NEGATIVE GLUTAMIDOTRANS-RXN-reactionStatus=TRUE_NEGATIVE

D-erythro-imidazole-glycerol-phosphate aminoimidazole carboxamide ribonucleotide

IMIDPHOSDEHYD-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P06633-TRUE_POSITIVE-1.89702e-109 HMM-P06633-TRUE_POSITIVE-1.9e-133

imidazole acetol-phosphate

HISTAMINOTRANS-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P07172-TRUE_POSITIVE-1.17597e-109 BLAST-P00815-FALSE_POSITIVE-2.09085e-95 HMM-P07172-TRUE_POSITIVE-4.3e-104 HMM-P47039-FALSE_POSITIVE-6.1e-07

L-histidinol-phosphate

HISTIDPHOS-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P06633-FALSE_POSITIVE-1.10407e-41 HMM-P06633-FALSE_POSITIVE-3.3e-25

histidinol

HISTOLDEHYD-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P00815-TRUE_POSITIVE-0 BLAST-P07172-FALSE_POSITIVE-1.01768e-46 HMM-P00815-TRUE_POSITIVE-1.8e-245

histidinal

HISTALDEHYD-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P00815-TRUE_POSITIVE-0 BLAST-P07172-FALSE_POSITIVE-1.01768e-46 HMM-P00815-TRUE_POSITIVE-1.8e-245

L-histidine

Pathway ID: HISTIDINE-SYN-Saccharomyces cerevisiae L-serine L-homocysteine

MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P32771-FALSE_POSITIVE-3.01743e-85 BLAST-P38715-FALSE_POSITIVE-5.93767e-64 BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-Q12458-FALSE_POSITIVE-2.3e-81 HMM-P38715-FALSE_POSITIVE-7.3e-68 HMM-P38115-FALSE_POSITIVE-1.5e-53 HMM-Q04894-TRUE_POSITIVE-1.4e-49 HMM-P25377-TRUE_POSITIVE-1e-43 HMM-P47137-FALSE_POSITIVE-5.6e-23 CYSTATHIONINE-BETA-SYNTHASE-RXN-reactionStatus=TRUE_POSITIVE CYSTATHIONINE-BETA-SYNTHASE-RXN-reactionStatus=TRUE_POSITIVE HMM-Q07551-FALSE_POSITIVE-3.2e-14 List of predictions: List of predictions: HMM-P00331-FALSE_POSITIVE-1.9e-12 BLAST-P32582-TRUE_POSITIVE-6.87031e-108 BLAST-P32582-TRUE_POSITIVE-6.87031e-108 HMM-P00330-FALSE_POSITIVE-1.5e-11 BLAST-O94073-POSSIBLE_POSITIVE-1.26365e-106 BLAST-O94073-POSSIBLE_POSITIVE-1.26365e-106 HMM-P38113-FALSE_POSITIVE-2.5e-11 HMM-P32582-TRUE_POSITIVE-1.1e-97 HMM-P32582-TRUE_POSITIVE-1.1e-97 HMM-P07246-FALSE_POSITIVE-4.9e-11 HMM-O94073-POSSIBLE_POSITIVE-2.9e-95 HMM-O94073-POSSIBLE_POSITIVE-2.9e-95 HMM-Q07786-FALSE_POSITIVE-2.3e-10 HMM-P53206-FALSE_POSITIVE-9.8e-05 HMM-P53206-FALSE_POSITIVE-9.8e-05 HMM-P35497-FALSE_POSITIVE-2.4e-10 HMM-Q07993-FALSE_POSITIVE-3.5e-10 HMM-P32771-FALSE_POSITIVE-4.7e-09 HMM-P39713-FALSE_POSITIVE-1.1e-06 HMM-P39714-FALSE_POSITIVE-2.9e-06 HMM-Q6B208-FALSE_POSITIVE-2.9e-06

MARIBOES-1.1.1.276-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-Q05016-FALSE_POSITIVE-1.8e-45 HMM-P40580-FALSE_POSITIVE-1.2e-05 HMM-Q54AB5-FALSE_POSITIVE-1.2e-05 HMM-P40579-FALSE_POSITIVE-2.1e-05 HMM-P40471-FALSE_POSITIVE-5.6e-05 HMM-Q45U07-FALSE_POSITIVE-5.8e-05

2-aminomalonate-semialdehyde cystathionine

CYSTAGLY-RXN-reactionStatus=TRUE_POSITIVE CYSTAGLY-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P31373-TRUE_POSITIVE-1.999e-101 BLAST-P31373-TRUE_POSITIVE-1.999e-101 BLAST-P53101-FALSE_POSITIVE-2.11097e-54 BLAST-P53101-FALSE_POSITIVE-2.11097e-54 BLAST-P43623-FALSE_POSITIVE-1.73391e-42 BLAST-P43623-FALSE_POSITIVE-1.73391e-42 HMM-P31373-TRUE_POSITIVE-1.6e-150 HMM-P31373-TRUE_POSITIVE-1.6e-150 HMM-P53101-FALSE_POSITIVE-4.3e-38 HMM-P53101-FALSE_POSITIVE-4.3e-38 HMM-P06106-FALSE_POSITIVE-7e-35 HMM-P06106-FALSE_POSITIVE-7e-35 HMM-P43623-FALSE_POSITIVE-3.2e-12 HMM-P43623-FALSE_POSITIVE-3.2e-12 HMM-P38716-FALSE_POSITIVE-5.1e-12 HMM-P38716-FALSE_POSITIVE-5.1e-12

2-oxobutanoate L-cysteine

MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: List of predictions: List of predictions: BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P00175-TRUE_POSITIVE-5.46824e-166 BLAST-P00175-TRUE_POSITIVE-5.46824e-166 MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-P16387-FALSE_POSITIVE-8e-13 HMM-P16387-FALSE_POSITIVE-8e-13 HMM-Q07540-FALSE_POSITIVE-1.2e-09 HMM-Q07540-FALSE_POSITIVE-1.2e-09

propionyl-CoA 2-hydroxybutyrate N-acetyl-L-cysteine

Pathway ID: HOMOCYSTEINE-DEG-Saccharomyces cerevisiae S-2-methyl-butyryl-CoA 2-methylbutanal

MARIBOES-1.1.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P38113-TRUE_POSITIVE-0 BLAST-P38113-TRUE_POSITIVE-0 BLAST-P07246-TRUE_POSITIVE-1.19444e-169 BLAST-P07246-TRUE_POSITIVE-1.19444e-169 BLAST-P00331-TRUE_POSITIVE-2.2163e-166 BLAST-P00331-TRUE_POSITIVE-2.2163e-166 BLAST-P00330-TRUE_POSITIVE-3.09529e-165 BLAST-P00330-TRUE_POSITIVE-3.09529e-165 BLAST-P10127-TRUE_POSITIVE-3.11897e-131 BLAST-P10127-TRUE_POSITIVE-3.11897e-131 BLAST-P32771-TRUE_POSITIVE-1.62685e-123 BLAST-P32771-TRUE_POSITIVE-1.62685e-123 BLAST-Q04018-FALSE_POSITIVE-2.98645e-81 BLAST-Q04018-FALSE_POSITIVE-2.98645e-81 HMM-P32771-TRUE_POSITIVE-1e-121 HMM-P32771-TRUE_POSITIVE-1e-121 HMM-P00331-TRUE_POSITIVE-3.2e-112 HMM-P00331-TRUE_POSITIVE-3.2e-112 HMM-P00330-TRUE_POSITIVE-6.9e-111 HMM-P00330-TRUE_POSITIVE-6.9e-111 HMM-P07246-TRUE_POSITIVE-4.8e-110 HMM-P07246-TRUE_POSITIVE-4.8e-110 HMM-P38113-TRUE_POSITIVE-1.7e-106 HMM-P38113-TRUE_POSITIVE-1.7e-106 HMM-Q07993-FALSE_POSITIVE-4.5e-26 HMM-Q07993-FALSE_POSITIVE-4.5e-26 HMM-Q04894-FALSE_POSITIVE-2.9e-23 HMM-Q04894-FALSE_POSITIVE-2.9e-23 HMM-P35497-FALSE_POSITIVE-9.5e-21 HMM-P35497-FALSE_POSITIVE-9.5e-21 HMM-Q07786-FALSE_POSITIVE-9.8e-21 HMM-Q07786-FALSE_POSITIVE-9.8e-21 HMM-P25377-FALSE_POSITIVE-4.1e-15 HMM-P25377-FALSE_POSITIVE-4.1e-15 HMM-P39713-FALSE_POSITIVE-5.8e-08 HMM-P39713-FALSE_POSITIVE-5.8e-08 HMM-Q6B208-FALSE_POSITIVE-1.3e-06 HMM-Q6B208-FALSE_POSITIVE-1.3e-06 HMM-P38230-FALSE_POSITIVE-1.5e-06 HMM-P38230-FALSE_POSITIVE-1.5e-06 HMM-P39714-FALSE_POSITIVE-2.5e-06 HMM-P39714-FALSE_POSITIVE-2.5e-06

2KETO-3METHYLVALERATE-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: List of predictions: List of predictions: MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P32771-FALSE_POSITIVE-3.01743e-85 BLAST-P32771-FALSE_POSITIVE-3.01743e-85 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 List of predictions: 2-MEBUCOA-FAD-RXN-reactionStatus=TRUE_NEGATIVE BLAST-P38715-FALSE_POSITIVE-5.93767e-64 BLAST-P38715-FALSE_POSITIVE-5.93767e-64 HMM-P32473-FALSE_POSITIVE-1.1e-55 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 HMM-P16387-FALSE_POSITIVE-5.1e-10 HMM-P32473-FALSE_POSITIVE-1.1e-55 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 HMM-P16387-FALSE_POSITIVE-5.1e-10 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-Q12458-FALSE_POSITIVE-2.3e-81 HMM-Q12458-FALSE_POSITIVE-2.3e-81 HMM-P38715-FALSE_POSITIVE-7.3e-68 HMM-P38715-FALSE_POSITIVE-7.3e-68 HMM-P38115-FALSE_POSITIVE-1.5e-53 HMM-P38115-FALSE_POSITIVE-1.5e-53 HMM-Q04894-TRUE_POSITIVE-1.4e-49 HMM-Q04894-TRUE_POSITIVE-1.4e-49 HMM-P25377-TRUE_POSITIVE-1e-43 HMM-P25377-TRUE_POSITIVE-1e-43 HMM-P47137-FALSE_POSITIVE-5.6e-23 HMM-P47137-FALSE_POSITIVE-5.6e-23 HMM-Q07551-FALSE_POSITIVE-6.1e-13 HMM-Q07551-FALSE_POSITIVE-6.1e-13 HMM-Q07786-FALSE_POSITIVE-3.7e-12 HMM-Q07786-FALSE_POSITIVE-3.7e-12 HMM-P35497-FALSE_POSITIVE-3.9e-12 HMM-P35497-FALSE_POSITIVE-3.9e-12 HMM-P00331-FALSE_POSITIVE-4.2e-12 HMM-P00331-FALSE_POSITIVE-4.2e-12 HMM-Q07993-FALSE_POSITIVE-5.9e-12 HMM-Q07993-FALSE_POSITIVE-5.9e-12 HMM-P00330-FALSE_POSITIVE-3.2e-11 HMM-P00330-FALSE_POSITIVE-3.2e-11 HMM-P38113-FALSE_POSITIVE-5.3e-11 HMM-P38113-FALSE_POSITIVE-5.3e-11 HMM-P07246-FALSE_POSITIVE-1e-10 HMM-P07246-FALSE_POSITIVE-1e-10 HMM-P32771-FALSE_POSITIVE-1.2e-10 HMM-P32771-FALSE_POSITIVE-1.2e-10 HMM-P39714-FALSE_POSITIVE-1.9e-07 HMM-P39714-FALSE_POSITIVE-1.9e-07 HMM-Q6B208-FALSE_POSITIVE-2e-07 HMM-Q6B208-FALSE_POSITIVE-2e-07 HMM-P39713-FALSE_POSITIVE-4e-07 HMM-P39713-FALSE_POSITIVE-4e-07 HMM-P38230-FALSE_POSITIVE-0.00022 HMM-P38230-FALSE_POSITIVE-0.00022

MARIBOES-1.1.1.265-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-1.1.1.265-RXN-reactionStatus=TRUE_NEGATIVE

2-keto-3-methyl-valerate tiglyl-CoA 2-methylbutanol

BRANCHED-CHAINAMINOTRANSFERILEU-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE HMM-P47176-TRUE_POSITIVE-3.7e-162 TIGLYLCOA-HYDROXY-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-P38891-TRUE_POSITIVE-7.5e-157 List of predictions: BLAST-P47176-TRUE_POSITIVE-1.49811e-110 HMM-P28817-FALSE_POSITIVE-2.8e-08 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-Q08558-FALSE_POSITIVE-0.00025 HMM-P47176-TRUE_POSITIVE-3.7e-162 MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE HMM-Q05871-FALSE_POSITIVE-0.00055 HMM-P38891-TRUE_POSITIVE-7.5e-157 List of predictions: BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P38891-TRUE_POSITIVE-7.5e-157

L-isoleucine 2-methyl-3-hydroxybutyryl-CoA

1.1.1.178-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-Q02207-FALSE_POSITIVE-1.1e-06 HMM-Q07530-FALSE_POSITIVE-7.5e-06 HMM-P32573-FALSE_POSITIVE-3.1e-05 HMM-P40580-FALSE_POSITIVE-0.00049 HMM-Q54AB5-FALSE_POSITIVE-0.00049

pyruvate 2-methylacetoacetyl-CoA

METHYLACETOACETYLCOATHIOL-RXN-reactionStatus=TRUE_POSITIVE METHYLACETOACETYLCOATHIOL-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: List of predictions: List of predictions: BLAST-P41338-TRUE_POSITIVE-0 BLAST-P41338-TRUE_POSITIVE-0 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P27796-FALSE_POSITIVE-1.92502e-67 BLAST-P27796-FALSE_POSITIVE-1.92502e-67 HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P41338-TRUE_POSITIVE-2.9e-61 HMM-P41338-TRUE_POSITIVE-2.9e-61 HMM-P16387-FALSE_POSITIVE-5.1e-10 HMM-P27796-FALSE_POSITIVE-3.5e-10 HMM-P27796-FALSE_POSITIVE-3.5e-10

acetyl-CoA propionyl-CoA

MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE

MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: List of predictions: List of predictions: MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 List of predictions: List of predictions: BLAST-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P16387-FALSE_POSITIVE-5.1e-10 HMM-P16387-FALSE_POSITIVE-5.1e-10 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-2e-09 HMM-P38137-FALSE_POSITIVE-2e-09 HMM-P38137-FALSE_POSITIVE-2e-09 HMM-P38137-FALSE_POSITIVE-2e-09

acetate propionate 2-oxobutanoate

Pathway ID: ISOLEUCINE-DEG-Saccharomyces cerevisiae pyruvate

MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P32473-FALSE_POSITIVE-2.33193e-65 HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P16387-FALSE_POSITIVE-8e-10

acetyl-CoA

MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE

MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE ACETYL-COA-ACETYLTRANSFER-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: List of predictions: BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-P41338-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P27796-FALSE_POSITIVE-9.02747e-61 BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P41338-TRUE_POSITIVE-1e-266 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P27796-FALSE_POSITIVE-1.5e-89 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-1.1e-09 HMM-P38137-FALSE_POSITIVE-1.1e-09

HYDROXYMETHYLGLUTARYL-COA-SYNTHASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P54839-TRUE_POSITIVE-2.28368e-125 HMM-P54839-TRUE_POSITIVE-6.4e-251 acetate acetoacetyl-CoA HMM-P34161-FALSE_POSITIVE-1.4e-05 HMM-P07269-FALSE_POSITIVE-4.8e-05 HMM-Q04116-FALSE_POSITIVE-0.00013 HMM-Q06858-FALSE_POSITIVE-0.00019

HYDROXYMETHYLGLUTARYL-COA-SYNTHASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P54839-TRUE_POSITIVE-2.28368e-125 HMM-P54839-TRUE_POSITIVE-6.4e-251 HMM-P34161-FALSE_POSITIVE-1.4e-05 HMM-P07269-FALSE_POSITIVE-4.8e-05 HMM-Q04116-FALSE_POSITIVE-0.00013 HMM-Q06858-FALSE_POSITIVE-0.00019

3-hydroxy-3-methyl-glutaryl-CoA

1.1.1.34-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-Q6B2D0-FALSE_POSITIVE-0 BLAST-P12683-TRUE_POSITIVE-0 BLAST-P12684-TRUE_POSITIVE-0 HMM-P12683-TRUE_POSITIVE-0 HMM-P12684-TRUE_POSITIVE-0 HMM-Q6B2D0-FALSE_POSITIVE-0

(R)-mevalonate

MEVALONATE-KINASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: HMM-P07277-TRUE_POSITIVE-1.4e-72

mevalonate-5P

PHOSPHOMEVALONATE-KINASE-RXN-reactionStatus=FALSE_NEGATIVE

mevalonate-5-PP

DIPHOSPHOMEVALONTE-DECARBOXYLASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P32377-TRUE_POSITIVE-4.87893e-87 HMM-P32377-TRUE_POSITIVE-1.8e-122

isopentenyl diphosphate

IPPISOM-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P15496-TRUE_POSITIVE-1.03436e-70 HMM-P15496-TRUE_POSITIVE-7.1e-79 HMM-P00175-FALSE_POSITIVE-1.1e-06

dimethylallyl diphosphate

Pathway ID: ISOPRENOIDS-Saccharomyces cerevisiae isovaleryl-CoA 3-methylbutanal

MARIBOES-1.1.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P38113-TRUE_POSITIVE-0 BLAST-P38113-TRUE_POSITIVE-0 BLAST-P07246-TRUE_POSITIVE-1.19444e-169 BLAST-P07246-TRUE_POSITIVE-1.19444e-169 BLAST-P00331-TRUE_POSITIVE-2.2163e-166 BLAST-P00331-TRUE_POSITIVE-2.2163e-166 BLAST-P00330-TRUE_POSITIVE-3.09529e-165 BLAST-P00330-TRUE_POSITIVE-3.09529e-165 BLAST-P10127-TRUE_POSITIVE-3.11897e-131 BLAST-P10127-TRUE_POSITIVE-3.11897e-131 BLAST-P32771-TRUE_POSITIVE-1.62685e-123 BLAST-P32771-TRUE_POSITIVE-1.62685e-123 BLAST-Q04018-FALSE_POSITIVE-2.98645e-81 BLAST-Q04018-FALSE_POSITIVE-2.98645e-81 HMM-P32771-TRUE_POSITIVE-1e-121 HMM-P32771-TRUE_POSITIVE-1e-121 HMM-P00331-TRUE_POSITIVE-3.2e-112 HMM-P00331-TRUE_POSITIVE-3.2e-112 HMM-P00330-TRUE_POSITIVE-6.9e-111 HMM-P00330-TRUE_POSITIVE-6.9e-111 HMM-P07246-TRUE_POSITIVE-4.8e-110 HMM-P07246-TRUE_POSITIVE-4.8e-110 HMM-P38113-TRUE_POSITIVE-1.7e-106 HMM-P38113-TRUE_POSITIVE-1.7e-106 HMM-Q07993-FALSE_POSITIVE-4.5e-26 HMM-Q07993-FALSE_POSITIVE-4.5e-26 HMM-Q04894-FALSE_POSITIVE-2.9e-23 HMM-Q04894-FALSE_POSITIVE-2.9e-23 HMM-P35497-FALSE_POSITIVE-9.5e-21 HMM-P35497-FALSE_POSITIVE-9.5e-21 HMM-Q07786-FALSE_POSITIVE-9.8e-21 HMM-Q07786-FALSE_POSITIVE-9.8e-21 HMM-P25377-FALSE_POSITIVE-4.1e-15 HMM-P25377-FALSE_POSITIVE-4.1e-15 HMM-P39713-FALSE_POSITIVE-3.2e-08 HMM-P39713-FALSE_POSITIVE-3.2e-08 HMM-Q6B208-FALSE_POSITIVE-7.7e-07 HMM-Q6B208-FALSE_POSITIVE-7.7e-07 HMM-P38230-FALSE_POSITIVE-8.9e-07 HMM-P38230-FALSE_POSITIVE-8.9e-07 HMM-P39714-FALSE_POSITIVE-1.6e-06 HMM-P39714-FALSE_POSITIVE-1.6e-06

2KETO-4METHYL-PENTANOATE-DEHYDROG-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE List of predictions: MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: List of predictions: BLAST-P32473-FALSE_POSITIVE-2.33193e-65 List of predictions: BLAST-P32771-FALSE_POSITIVE-3.01743e-85 BLAST-P32771-FALSE_POSITIVE-3.01743e-85 ISOVALERYL-COA-FAD-RXN-reactionStatus=FALSE_NEGATIVE HMM-P32473-FALSE_POSITIVE-1.1e-55 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P38715-FALSE_POSITIVE-5.93767e-64 BLAST-P38715-FALSE_POSITIVE-5.93767e-64 HMM-P16387-FALSE_POSITIVE-1.4e-13 HMM-P32473-FALSE_POSITIVE-1.1e-55 BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 HMM-P16387-FALSE_POSITIVE-1.4e-13 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-Q12458-FALSE_POSITIVE-2.3e-81 HMM-Q12458-FALSE_POSITIVE-2.3e-81 HMM-P38715-FALSE_POSITIVE-7.3e-68 HMM-P38715-FALSE_POSITIVE-7.3e-68 HMM-P38115-FALSE_POSITIVE-1.5e-53 HMM-P38115-FALSE_POSITIVE-1.5e-53 HMM-Q04894-TRUE_POSITIVE-1.4e-49 HMM-Q04894-TRUE_POSITIVE-1.4e-49 HMM-P25377-TRUE_POSITIVE-1e-43 HMM-P25377-TRUE_POSITIVE-1e-43 HMM-P47137-FALSE_POSITIVE-5.6e-23 HMM-P47137-FALSE_POSITIVE-5.6e-23 HMM-Q07551-FALSE_POSITIVE-3.2e-17 HMM-Q07551-FALSE_POSITIVE-3.2e-17 HMM-P00331-FALSE_POSITIVE-7.6e-12 HMM-P00331-FALSE_POSITIVE-7.6e-12 HMM-P00330-FALSE_POSITIVE-3e-10 HMM-P00330-FALSE_POSITIVE-3e-10 HMM-Q07786-FALSE_POSITIVE-3.8e-10 HMM-Q07786-FALSE_POSITIVE-3.8e-10 HMM-P35497-FALSE_POSITIVE-4e-10 HMM-P35497-FALSE_POSITIVE-4e-10 HMM-P38113-FALSE_POSITIVE-4.8e-10 HMM-P38113-FALSE_POSITIVE-4.8e-10 HMM-Q07993-FALSE_POSITIVE-5.6e-10 HMM-Q07993-FALSE_POSITIVE-5.6e-10 HMM-P07246-FALSE_POSITIVE-8.7e-10 HMM-P07246-FALSE_POSITIVE-8.7e-10 HMM-P32771-FALSE_POSITIVE-7.3e-09 HMM-P32771-FALSE_POSITIVE-7.3e-09 HMM-P39714-FALSE_POSITIVE-3.9e-06 HMM-P39714-FALSE_POSITIVE-3.9e-06 HMM-Q6B208-FALSE_POSITIVE-4e-06 HMM-Q6B208-FALSE_POSITIVE-4e-06 HMM-P39713-FALSE_POSITIVE-7.1e-06 HMM-P39713-FALSE_POSITIVE-7.1e-06

MARIBOES-1.1.1.265-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-1.1.1.265-RXN-reactionStatus=TRUE_NEGATIVE

2-ketoisocaproate 3-methylcrotonyl-CoA 3-methylbutanol

BRANCHED-CHAINAMINOTRANSFERLEU-RXN-reactionStatus=TRUE_POSITIVE List of predictions: METHYLCROTONYL-COA-CARBOXYLASE-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P47176-TRUE_POSITIVE-1.49811e-110 List of predictions: BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P32528-FALSE_POSITIVE-2.69609e-108 MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE HMM-P47176-TRUE_POSITIVE-8.1e-153 BLAST-P32327-FALSE_POSITIVE-5.78079e-92 List of predictions: HMM-P38891-TRUE_POSITIVE-2.2e-146 BLAST-P11154-FALSE_POSITIVE-4.34614e-89 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P32874-FALSE_POSITIVE-2.8412e-67 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-Q00955-FALSE_POSITIVE-1.42354e-62 HMM-P47176-TRUE_POSITIVE-3.7e-162 MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE HMM-P32528-FALSE_POSITIVE-2.3e-91 HMM-P38891-TRUE_POSITIVE-7.5e-157 List of predictions: HMM-P11154-FALSE_POSITIVE-1.3e-79 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 HMM-P32327-FALSE_POSITIVE-2e-79 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-Q00955-FALSE_POSITIVE-2.4e-25 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P32874-FALSE_POSITIVE-1.2e-23 HMM-P38891-TRUE_POSITIVE-7.5e-157

L-leucine 3-methylglutaconyl-CoA

LEUCINE-23-AMINOMUTASE-RXN-reactionStatus=TRUE_NEGATIVE METHYLGLUTACONYL-COA-HYDRATASE-RXN-reactionStatus=FALSE_NEGATIVE

β-leucine 3-hydroxy-3-methyl-glutaryl-CoA

RXN-7690-reactionStatus=TRUE_NEGATIVE HYDROXYMETHYLGLUTARYL-COA-LYASE-RXN-reactionStatus=FALSE_NEGATIVE

β-ketoisocaproate acetoacetate

RXN-7691-reactionStatus=TRUE_NEGATIVE RXN-7691-reactionStatus=TRUE_NEGATIVE

isobutyrate acetate

MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: List of predictions: List of predictions: BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-6.4e-09 HMM-P38137-FALSE_POSITIVE-6.4e-09 HMM-P38137-FALSE_POSITIVE-6.4e-09 HMM-P38137-FALSE_POSITIVE-6.4e-09

isobutyryl-CoA acetyl-CoA

Pathway ID: LEUCINE-DEG-Saccharomyces cerevisiae L-lysine

LYSINE-23-AMINOMUTASE-RXN-reactionStatus=FALSE_NEGATIVE 1.5.1.8-RXN-reactionStatus=POSSIBLE_NEGATIVE LYSINE-RACEMASE-RXN-reactionStatus=TRUE_NEGATIVE LYSACET-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE LYSDECARBOX-RXN-reactionStatus=FALSE_NEGATIVE

(3S)-3,6-diaminohexanoate D-lysine LYSINE-2-MONOOXYGENASE-RXN-reactionStatus=TRUE_NEGATIVE N6-acetyl-L-lysine N2-acetyl-L-Lysine cadaverine

L-LYSINE-OXIDASE-RXN-reactionStatus=TRUE_NEGATIVE ACETCAPR-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE List of predictions: MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P47176-TRUE_POSITIVE-1.49811e-110 List of predictions: BETA-LYSINE-56-AMINOMUTASE-RXN-reactionStatus=TRUE_NEGATIVE saccharopine BLAST-P47176-TRUE_POSITIVE-1.49811e-110 RXN-8163-reactionStatus=TRUE_NEGATIVE BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-P47176-TRUE_POSITIVE-3.7e-162 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P38891-TRUE_POSITIVE-7.5e-157

(3S,5S)-3,5-diaminohexanoate pyruvate Δ1-piperideine-2-carboxylate 2-keto-6-acetamidocaproate

L-LYSINE-AMINOTRANSFERASE-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P17649-FALSE_POSITIVE-1.17741e-41 HMM-A5H0J7-FALSE_POSITIVE-9.5e-18 HMM-P17649-FALSE_POSITIVE-1.5e-17 HMM-P18544-FALSE_POSITIVE-3.8e-11 MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE HMM-P07991-FALSE_POSITIVE-1.1e-10 List of predictions: HMM-Q4R1J1-FALSE_POSITIVE-4.6e-06 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 1.4.1.11-RXN-reactionStatus=TRUE_NEGATIVE HMM-P50277-FALSE_POSITIVE-4.9e-06 RXN-8166-reactionStatus=TRUE_NEGATIVE RXN-8172-reactionStatus=TRUE_NEGATIVE RXN-8172-reactionStatus=TRUE_NEGATIVE 5-aminopentanamide KETAMID-RXN-reactionStatus=TRUE_NEGATIVE HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-Q66R22-FALSE_POSITIVE-5.4e-06 HMM-P16387-FALSE_POSITIVE-7.9e-11 HMM-Q5DWF2-FALSE_POSITIVE-4.6e-05 HMM-Q5DWF5-FALSE_POSITIVE-6e-05 HMM-Q4R1J2-FALSE_POSITIVE-8e-05

RXN-8808-reactionStatus=POSSIBLE_NEGATIVE

LYSINE--PYRUVATE-6-AMINOTRANSFERASE-RXN-reactionStatus=TRUE_NEGATIVE

(S)-5-amino-3-oxohexanoate acetyl-CoA 1.5.1.9-RXN-reactionStatus=FALSE_NEGATIVE L-pipecolate 2-keto-6-aminocaproate 5-AMINOPENTANAMIDASE-RXN-reactionStatus=TRUE_NEGATIVE 5-acetamidovalerate

R125-RXN-reactionStatus=TRUE_NEGATIVE R125-RXN-reactionStatus=TRUE_NEGATIVE R125-RXN-reactionStatus=TRUE_NEGATIVE R125-RXN-reactionStatus=TRUE_NEGATIVE PHOSACETYLTRANS-RXN-reactionStatus=FALSE_NEGATIVE RXN-8161-reactionStatus=TRUE_NEGATIVE RXN-8243-reactionStatus=TRUE_NEGATIVE AMVAL-RXN-reactionStatus=TRUE_NEGATIVE

MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE

MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 L-3-aminobutyryl-CoA acetylphosphate (S)-2,3,4,5-tetrahydropiperidine-2-carboxylate 5-aminopentanoate BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-5.7e-08 HMM-P38137-FALSE_POSITIVE-5.7e-08

RXN-8173-reactionStatus=TRUE_NEGATIVE VAGL-RXN-reactionStatus=TRUE_NEGATIVE 4.3.1.14-RXN-reactionStatus=TRUE_NEGATIVE acetoacetate ACETATEKIN-RXN-reactionStatus=FALSE_NEGATIVE RXN-8173-reactionStatus=TRUE_NEGATIVE RXN-8816-reactionStatus=TRUE_NEGATIVE 5-AMINOVALERATE-AMINOTRANSFERASE-RXN-reactionStatus=TRUE_NEGATIVE

RXN-8162-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P07702-TRUE_POSITIVE-0 BLAST-P54115-FALSE_POSITIVE-3.91214e-53 BLAST-A9LRZ7-FALSE_POSITIVE-3.91214e-53 BLAST-P46367-FALSE_POSITIVE-3.36854e-51 BLAST-P40047-FALSE_POSITIVE-4.70722e-48 BLAST-P38067-FALSE_POSITIVE-1.74452e-47 BLAST-P32872-FALSE_POSITIVE-4.12373e-44 ACETYL-COA-ACETYLTRANSFER-RXN-reactionStatus=TRUE_POSITIVE BLAST-P47771-FALSE_POSITIVE-1.15113e-42 List of predictions: BLAST-P54114-FALSE_POSITIVE-5.08462e-41 BLAST-P41338-TRUE_POSITIVE-0 HMM-P54115-FALSE_POSITIVE-6.5e-23 crotonyl-CoA BLAST-P27796-FALSE_POSITIVE-9.02747e-61 acetate 2-aminoadipate-6-semialdehyde HMM-A9LRZ7-FALSE_POSITIVE-6.5e-23 HMM-P41338-TRUE_POSITIVE-1e-266 HMM-P46367-FALSE_POSITIVE-4.2e-19 HMM-P27796-FALSE_POSITIVE-1.5e-89 HMM-P40047-FALSE_POSITIVE-1.3e-15 HMM-P38067-FALSE_POSITIVE-2.7e-14 HMM-P47771-FALSE_POSITIVE-2.1e-13 HMM-P54114-FALSE_POSITIVE-4.3e-13 HMM-P32872-FALSE_POSITIVE-7.2e-13 HMM-P07275-FALSE_POSITIVE-1.6e-08 HMM-P38694-FALSE_POSITIVE-1.2e-07 HMM-Q04458-FALSE_POSITIVE-2.6e-05 HMM-P22281-FALSE_POSITIVE-0.00056

ALLYSINE-DEHYDROG-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P07702-TRUE_POSITIVE-0 BLAST-P54115-FALSE_POSITIVE-3.91214e-53 BLAST-A9LRZ7-FALSE_POSITIVE-3.91214e-53 BLAST-P46367-FALSE_POSITIVE-3.36854e-51 BLAST-P40047-FALSE_POSITIVE-4.70722e-48 BLAST-P38067-FALSE_POSITIVE-1.74452e-47 BLAST-P32872-FALSE_POSITIVE-4.12373e-44 BLAST-P47771-FALSE_POSITIVE-1.15113e-42 BLAST-P54114-FALSE_POSITIVE-5.08462e-41 R22-RXN-reactionStatus=FALSE_NEGATIVE 2.8.3.9-RXN-reactionStatus=FALSE_NEGATIVE 2.8.3.9-RXN-reactionStatus=FALSE_NEGATIVE HMM-P54115-FALSE_POSITIVE-6.5e-23 glutarate semialdehyde HMM-A9LRZ7-FALSE_POSITIVE-6.5e-23 HMM-P46367-FALSE_POSITIVE-4.2e-19 HMM-P40047-FALSE_POSITIVE-1.3e-15 HMM-P38067-FALSE_POSITIVE-1.2e-13 HMM-P47771-FALSE_POSITIVE-2e-10 HMM-P54114-FALSE_POSITIVE-3.6e-10 HMM-P32872-FALSE_POSITIVE-5.4e-10 HMM-P07275-FALSE_POSITIVE-1.8e-06 HMM-P38694-FALSE_POSITIVE-9e-06 HMM-Q04458-FALSE_POSITIVE-0.00068

butyryl-CoA α-aminoadipate

2.8.3.9-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE 2-AMINOADIPATE-AMINOTRANSFERASE-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: List of predictions: List of predictions: BLAST-Q66RJ0-FALSE_POSITIVE-0 List of predictions: BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P53090-FALSE_POSITIVE-1.38648e-52 GLUTARATE-SEMIALDEHYDE-DEHYDROGENASE-RXN-reactionStatus=TRUE_NEGATIVE BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P52910-TRUE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 2.8.3.9-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-P53090-FALSE_POSITIVE-8.5e-40 HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P32473-FALSE_POSITIVE-1.1e-55 BLAST-Q01574-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P38840-FALSE_POSITIVE-5.5e-15 RXN-8182-reactionStatus=TRUE_NEGATIVE HMM-P16387-FALSE_POSITIVE-7.9e-11 HMM-P16387-FALSE_POSITIVE-7.9e-11 HMM-P52910-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P10356-FALSE_POSITIVE-1.1e-05 HMM-Q01574-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-5.7e-08 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-5.7e-08

2-ketopentanoate butyrate acetoacetyl-CoA α-ketoadipate

2-KETO-ADIPATE-DEHYDROG-RXN-reactionStatus=TRUE_NEGATIVE RXN-8167-reactionStatus=TRUE_NEGATIVE

2-KETO-ADIPATE-DEHYDROG-RXN-reactionStatus=TRUE_NEGATIVE CO2 glutarate

RXN-8164-reactionStatus=TRUE_NEGATIVE

glutaryl-CoA

Pathway ID: LYSINE-DEG-Saccharomyces cerevisiae L-methionine

S-ADENMETSYN-RXN-reactionStatus=TRUE_POSITIVE List of predictions: METHIONINE-GAMMA-LYASE-RXN-reactionStatus=FALSE_NEGATIVE METHIONINE-GAMMA-LYASE-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P19358-TRUE_POSITIVE-2.36136e-176 List of predictions: List of predictions: BLAST-Q6B194-POSSIBLE_POSITIVE-1.18175e-175 MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE HMM-P38128-FALSE_POSITIVE-1.1e-05 HMM-P38128-FALSE_POSITIVE-1.1e-05 BLAST-P10659-TRUE_POSITIVE-9.12946e-174 HMM-Q12224-FALSE_POSITIVE-1.9e-05 HMM-Q12224-FALSE_POSITIVE-1.9e-05 HMM-P10659-TRUE_POSITIVE-1.7e-260 HMM-P19358-TRUE_POSITIVE-3.8e-257 HMM-Q6B194-POSSIBLE_POSITIVE-1.2e-255

N-acetyl-DL-methionine methanethiol 2-oxobutanoate S-adenosyl-L-methionine

MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: List of predictions: List of predictions: BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P00175-TRUE_POSITIVE-5.46824e-166 BLAST-P00175-TRUE_POSITIVE-5.46824e-166 DNA-CYTOSINE-5--METHYLTRANSFERASE-RXN-reactionStatus=FALSE_NEGATIVE HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-P16387-FALSE_POSITIVE-5.3e-13 HMM-P16387-FALSE_POSITIVE-5.3e-13 HMM-Q07540-FALSE_POSITIVE-1.4e-08 HMM-Q07540-FALSE_POSITIVE-1.4e-08

propionyl-CoA 2-hydroxybutyrate S-adenosyl-L-homocysteine

ADENOSYLHOMOCYSTEINASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P39954-TRUE_POSITIVE-0 HMM-P39954-TRUE_POSITIVE-0

L-homocysteine

Pathway ID: METHIONINE-DEG-Saccharomyces cerevisiae D-lactaldehyde

RXN-8641-reactionStatus=FALSE_NEGATIVE List of predictions: MARIBOES-1.1.1.265-RXN-reactionStatus=TRUE_NEGATIVE BLAST-P10127-FALSE_POSITIVE-1.73403e-73 HMM-P10127-FALSE_POSITIVE-1.5e-75

L-1,2-propanediol D-1,2-propanediol

MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P32771-FALSE_POSITIVE-3.01743e-85 BLAST-P38715-FALSE_POSITIVE-5.93767e-64 D-LACTALDEHYDE-DEHYDROGENASE-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-1.1.1.265-RXN-reactionStatus=TRUE_NEGATIVE BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-Q12458-FALSE_POSITIVE-2.3e-81 HMM-P38715-FALSE_POSITIVE-7.3e-68 HMM-P38115-FALSE_POSITIVE-1.5e-53 HMM-Q04894-TRUE_POSITIVE-1.4e-49 HMM-P25377-TRUE_POSITIVE-1e-43 HMM-P47137-FALSE_POSITIVE-5.6e-23 HMM-P00331-FALSE_POSITIVE-5.7e-12 HMM-Q07551-FALSE_POSITIVE-7.9e-12 HMM-P00330-FALSE_POSITIVE-4.2e-11 HMM-P38113-FALSE_POSITIVE-7e-11 HMM-P07246-FALSE_POSITIVE-1.3e-10 HMM-Q07786-FALSE_POSITIVE-1e-09 HMM-P35497-FALSE_POSITIVE-1.1e-09 HMM-Q07993-FALSE_POSITIVE-1.5e-09 HMM-P32771-FALSE_POSITIVE-1.7e-08 HMM-P39713-FALSE_POSITIVE-2.4e-06 HMM-P39714-FALSE_POSITIVE-7.5e-06 HMM-Q6B208-FALSE_POSITIVE-7.7e-06

MARIBOES-1.1.1.265-RXN-reactionStatus=TRUE_NEGATIVE

L-lactaldehyde

RXN-8636-reactionStatus=FALSE_NEGATIVE List of predictions: MARIBOES-1.1.1.1-RXN-reactionStatus=TRUE_POSITIVE BLAST-P14065-FALSE_POSITIVE-1.75774e-55 List of predictions: BLAST-P38113-TRUE_POSITIVE-0 MARIBOES-1.1.1.1-RXN-reactionStatus=TRUE_POSITIVE BLAST-P07246-TRUE_POSITIVE-1.19444e-169 List of predictions: BLAST-P00331-TRUE_POSITIVE-2.2163e-166 BLAST-P38113-TRUE_POSITIVE-0 BLAST-P00330-TRUE_POSITIVE-3.09529e-165 BLAST-P07246-TRUE_POSITIVE-1.19444e-169 BLAST-P10127-TRUE_POSITIVE-3.11897e-131 BLAST-P00331-TRUE_POSITIVE-2.2163e-166 BLAST-P32771-TRUE_POSITIVE-1.62685e-123 BLAST-P00330-TRUE_POSITIVE-3.09529e-165 BLAST-Q04018-FALSE_POSITIVE-2.98645e-81 BLAST-P10127-TRUE_POSITIVE-3.11897e-131 HMM-P32771-TRUE_POSITIVE-1e-121 BLAST-P32771-TRUE_POSITIVE-1.62685e-123 HMM-P00331-TRUE_POSITIVE-3.2e-112 BLAST-Q04018-FALSE_POSITIVE-2.98645e-81 RXN-8632-reactionStatus=TRUE_NEGATIVE HMM-P00330-TRUE_POSITIVE-6.9e-111 HMM-P32771-TRUE_POSITIVE-1e-121 MARIBOES-1.1.1.4-RXN-reactionStatus=FALSE_NEGATIVE HMM-P07246-TRUE_POSITIVE-4.8e-110 HMM-P00331-TRUE_POSITIVE-3.2e-112 MARIBOES-1.1.1.4-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-P38113-TRUE_POSITIVE-1.7e-106 HMM-P00330-TRUE_POSITIVE-6.9e-111 List of predictions: BLAST-P25337-FALSE_POSITIVE-3.96292e-40 LACTALDEHYDE-OXI-RXN-reactionStatus=TRUE_NEGATIVE HMM-Q07993-FALSE_POSITIVE-4.5e-26 HMM-P07246-TRUE_POSITIVE-4.8e-110 BLAST-P25337-FALSE_POSITIVE-3.96292e-40 HMM-P25337-FALSE_POSITIVE-6e-57 HMM-Q04894-FALSE_POSITIVE-2.9e-23 HMM-P38113-TRUE_POSITIVE-1.7e-106 HMM-P25337-FALSE_POSITIVE-6e-57 HMM-P35497-FALSE_POSITIVE-9.5e-21 HMM-Q07993-FALSE_POSITIVE-4.5e-26 HMM-Q07786-FALSE_POSITIVE-9.8e-21 HMM-Q04894-FALSE_POSITIVE-2.9e-23 HMM-P25377-FALSE_POSITIVE-4.1e-15 HMM-P35497-FALSE_POSITIVE-9.5e-21 HMM-P39713-FALSE_POSITIVE-6.6e-07 HMM-Q07786-FALSE_POSITIVE-9.8e-21 HMM-Q6B208-FALSE_POSITIVE-0.00074 HMM-P25377-FALSE_POSITIVE-4.1e-15 HMM-P39713-FALSE_POSITIVE-6.6e-07 MARIBOES-1.1.1.4-RXN-reactionStatus=FALSE_NEGATIVE HMM-Q6B208-FALSE_POSITIVE-0.00074 List of predictions: BLAST-P25337-FALSE_POSITIVE-3.96292e-40 MARIBOES-1.1.1.4-RXN-reactionStatus=FALSE_NEGATIVE HMM-P25337-FALSE_POSITIVE-6e-57 List of predictions: BLAST-P25337-FALSE_POSITIVE-3.96292e-40 HMM-P25337-FALSE_POSITIVE-6e-57

methylglyoxal

MARIBOES-1.1.1.265-RXN-reactionStatus=TRUE_NEGATIVE

GLYOXIII-RXN-reactionStatus=TRUE_NEGATIVE S-lactoyl-glutathione acetol

LACTALDDEHYDROG-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P46367-FALSE_POSITIVE-6.67969e-80 GLYOXII-RXN-reactionStatus=TRUE_POSITIVE BLAST-P40047-FALSE_POSITIVE-1.99333e-78 List of predictions: METHYL-GLYOXAL-DEHYDROG-RXN-reactionStatus=TRUE_NEGATIVE BLAST-P38067-FALSE_POSITIVE-1.30438e-73 HMM-Q6Q5S8-FALSE_POSITIVE-7.7e-43 BLAST-A9LRZ7-FALSE_POSITIVE-2.04742e-72 RXN-8639-reactionStatus=TRUE_NEGATIVE HMM-Q05584-TRUE_POSITIVE-9.3e-43 BLAST-P54115-FALSE_POSITIVE-2.04742e-72 HMM-Q12320-TRUE_POSITIVE-4.7e-26 BLAST-P54114-FALSE_POSITIVE-1.00076e-66 BLAST-P47771-FALSE_POSITIVE-1.16327e-65

D-lactate

DLACTDEHYDROGFAD-RXN-reactionStatus=TRUE_POSITIVEDLACTDEHYDROGFAD-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P32891-TRUE_POSITIVE-0 BLAST-P32891-TRUE_POSITIVE-0 BLAST-P46681-TRUE_POSITIVE-1.0539e-152 BLAST-P46681-TRUE_POSITIVE-1.0539e-152 BLAST-Q07824-FALSE_POSITIVE-1.95626e-96 BLAST-Q07824-FALSE_POSITIVE-1.95626e-96 BLAST-Q06451-FALSE_POSITIVE-2.43302e-74 BLAST-Q06451-FALSE_POSITIVE-2.43302e-74 BLAST-P53283-FALSE_POSITIVE-3.04867e-73 BLAST-P53283-FALSE_POSITIVE-3.04867e-73 BLAST-Q12256-FALSE_POSITIVE-1.28496e-60 BLAST-Q12256-FALSE_POSITIVE-1.28496e-60 BLAST-P38776-FALSE_POSITIVE-6.37902e-59 BLAST-P38776-FALSE_POSITIVE-6.37902e-59 BLAST-P38124-FALSE_POSITIVE-4.75414e-55 BLAST-P38124-FALSE_POSITIVE-4.75414e-55 BLAST-P35200-FALSE_POSITIVE-4.38459e-42 BLAST-P35200-FALSE_POSITIVE-4.38459e-42 HMM-P32891-TRUE_POSITIVE-1.4e-256 HMM-P32891-TRUE_POSITIVE-1.4e-256 HMM-Q07824-FALSE_POSITIVE-4e-142 HMM-Q07824-FALSE_POSITIVE-4e-142 HMM-P53283-FALSE_POSITIVE-4.4e-54 HMM-P53283-FALSE_POSITIVE-4.4e-54 HMM-Q06451-FALSE_POSITIVE-3.8e-53 HMM-Q06451-FALSE_POSITIVE-3.8e-53 HMM-Q12256-FALSE_POSITIVE-4.7e-35 HMM-Q12256-FALSE_POSITIVE-4.7e-35 HMM-P38124-FALSE_POSITIVE-1.3e-24 HMM-P38124-FALSE_POSITIVE-1.3e-24 HMM-P38776-FALSE_POSITIVE-3.4e-24 HMM-P38776-FALSE_POSITIVE-3.4e-24 HMM-P46681-TRUE_POSITIVE-1.3e-10 HMM-P46681-TRUE_POSITIVE-1.3e-10 HMM-P39976-TRUE_POSITIVE-2.8e-09 HMM-P39976-TRUE_POSITIVE-2.8e-09 HMM-P38125-FALSE_POSITIVE-1.9e-06 HMM-P38125-FALSE_POSITIVE-1.9e-06 HMM-P38227-FALSE_POSITIVE-6.6e-05 HMM-P38227-FALSE_POSITIVE-6.6e-05

pyruvate Unknown-Quinols

MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: List of predictions: List of predictions: BLAST-P00175-TRUE_POSITIVE-5.46824e-166 BLAST-P00175-TRUE_POSITIVE-5.46824e-166 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-Q07540-FALSE_POSITIVE-3.1e-09 HMM-Q07540-FALSE_POSITIVE-3.1e-09 HMM-P16387-FALSE_POSITIVE-2.9e-10

L-lactate acetyl-CoA

Pathway ID: Methylglyoxal-Detoxification-Saccharomyces cerevisiae L-aspartate

L-ASPARTATE-OXID-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE BLAST-Q00711-FALSE_POSITIVE-2.51795e-63 List of predictions: List of predictions: BLAST-P47052-FALSE_POSITIVE-2.67017e-62 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 HMM-Q00711-FALSE_POSITIVE-5.3e-94 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-P47052-FALSE_POSITIVE-9.2e-92 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P21375-FALSE_POSITIVE-1.1e-14 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P32614-FALSE_POSITIVE-2.8e-13

2-amino-3-carboxymuconate semialdehyde α-iminosuccinate oxaloacetate

RXN-5721-reactionStatus=TRUE_NEGATIVE QUINOLINATE-SYNTHA-RXN-reactionStatus=FALSE_NEGATIVE

quinolinate

QUINOPRIBOTRANS-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P43619-TRUE_POSITIVE-4.31559e-65 HMM-P43619-TRUE_POSITIVE-1.2e-79

nicotinate mononucleotide

NICONUCADENYLYLTRAN-RXN-reactionStatus=FALSE_NEGATIVE

nicotinate adenine dinucleotide

NAD-SYNTH-GLN-RXN-reactionStatus=TRUE_POSITIVE List of predictions: HMM-P38795-TRUE_POSITIVE-3.8e-08

NAD-SYNTH-NH3-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-P38795-FALSE_POSITIVE-1.1e-08 HMM-P38625-FALSE_POSITIVE-2.8e-05

NICOTINATEPRIBOSYLTRANS-RXN-reactionStatus=TRUE_POSITIVE List of predictions: NAD+ NMNAMIDOHYDRO-RXN-reactionStatus=TRUE_NEGATIVE BLAST-P39683-TRUE_POSITIVE-1.05612e-68 HMM-P39683-TRUE_POSITIVE-1.3e-66

MARIBOES-2.7.7.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-2.7.7.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P38861-TRUE_POSITIVE-2.08026e-165 BLAST-P38861-TRUE_POSITIVE-2.08026e-165 BLAST-Q06178-TRUE_POSITIVE-2.73888e-118 BLAST-Q06178-TRUE_POSITIVE-2.73888e-118 BLAST-P53204-TRUE_POSITIVE-2.49942e-117 BLAST-P53204-TRUE_POSITIVE-2.49942e-117 BLAST-Q12129-TRUE_POSITIVE-3.98003e-74 BLAST-Q12129-TRUE_POSITIVE-3.98003e-74 NADNUCLEOSID-RXN-reactionStatus=FALSE_NEGATIVE HMM-P38861-TRUE_POSITIVE-3.5e-262 HMM-P38861-TRUE_POSITIVE-3.5e-262 HMM-Q12129-TRUE_POSITIVE-3.5e-95 HMM-Q12129-TRUE_POSITIVE-3.5e-95 HMM-P53204-TRUE_POSITIVE-1e-65 HMM-P53204-TRUE_POSITIVE-1e-65 HMM-Q06178-TRUE_POSITIVE-4.3e-63 HMM-Q06178-TRUE_POSITIVE-4.3e-63

NADPYROPHOSPHAT-RXN-reactionStatus=TRUE_POSITIVE 2.7.7.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: ATP HMM-P53164-TRUE_POSITIVE-4e-12 nicotinamide riboside nicotinamide BLAST-Q06178-TRUE_POSITIVE-5.06963e-45 HMM-Q6B192-FALSE_POSITIVE-4e-12

RIBOSYLNICOTINAMIDE-KINASE-RXN-reactionStatus=FALSE_NEGATIVE NMNNUCLEOSID-RXN-reactionStatus=TRUE_NEGATIVE 2.4.2.12-RXN-reactionStatus=FALSE_NEGATIVE NICOTINAMID-RXN-reactionStatus=FALSE_NEGATIVE

nicotinamide mononucleotide nicotinate

Pathway ID: NAD-SYN-Saccharomyces cerevisiae phenylpyruvate

PHEAMINOTRANS-RXN-reactionStatus=POSSIBLE_NEGATIVE MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE List of predictions: MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P47176-TRUE_POSITIVE-1.49811e-110 List of predictions: BLAST-P00175-TRUE_POSITIVE-5.46824e-166 BLAST-P00175-TRUE_POSITIVE-5.46824e-166 PHENYLPYRUVATE-DECARBOXYLASE-RXN-reactionStatus=TRUE_NEGATIVE BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-P47176-TRUE_POSITIVE-3.7e-162 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-Q07540-FALSE_POSITIVE-2.7e-08 HMM-Q07540-FALSE_POSITIVE-2.7e-08 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P38891-TRUE_POSITIVE-7.5e-157

phenylacetaldehyde phenyllactate L-phenylalanine

RXN-7700-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P38113-TRUE_POSITIVE-0 BLAST-P07246-TRUE_POSITIVE-1.19444e-169 BLAST-P00331-TRUE_POSITIVE-2.2163e-166 BLAST-P00330-TRUE_POSITIVE-3.09529e-165 BLAST-P10127-TRUE_POSITIVE-3.11897e-131 BLAST-P32771-TRUE_POSITIVE-1.62685e-123 BLAST-Q04018-FALSE_POSITIVE-2.98645e-81 HMM-P32771-TRUE_POSITIVE-1e-121 HMM-P00331-TRUE_POSITIVE-3.2e-112 HMM-P00330-TRUE_POSITIVE-6.9e-111 HMM-P07246-TRUE_POSITIVE-4.8e-110 MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE HMM-P38113-TRUE_POSITIVE-1.7e-106 List of predictions: HMM-Q07993-FALSE_POSITIVE-4.5e-26 BLAST-P32771-FALSE_POSITIVE-3.01743e-85 HMM-Q04894-FALSE_POSITIVE-2.9e-23 BLAST-P38715-FALSE_POSITIVE-5.93767e-64 HMM-P35497-FALSE_POSITIVE-9.5e-21 BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 HMM-Q07786-FALSE_POSITIVE-9.8e-21 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 HMM-P25377-FALSE_POSITIVE-4.1e-15 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 HMM-P39713-FALSE_POSITIVE-5.2e-07 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 HMM-Q6B208-FALSE_POSITIVE-8.3e-06 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 HMM-P38230-FALSE_POSITIVE-9.5e-06 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-P39714-FALSE_POSITIVE-1.6e-05 HMM-Q12458-FALSE_POSITIVE-2.3e-81 PHENDEHYD-RXN-reactionStatus=FALSE_NEGATIVE HMM-P38715-FALSE_POSITIVE-7.3e-68 List of predictions: HMM-P38115-FALSE_POSITIVE-1.5e-53 MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE BLAST-P46367-FALSE_POSITIVE-1.58552e-103 HMM-Q04894-TRUE_POSITIVE-1.4e-49 List of predictions: BLAST-P40047-FALSE_POSITIVE-3.36262e-100 HMM-P25377-TRUE_POSITIVE-1e-43 BLAST-P32771-FALSE_POSITIVE-3.01743e-85 BLAST-A9LRZ7-FALSE_POSITIVE-2.53794e-92 HMM-P47137-FALSE_POSITIVE-5.6e-23 PHENYLALANINE-4-MONOOXYGENASE-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P38715-FALSE_POSITIVE-5.93767e-64 BLAST-P54115-FALSE_POSITIVE-2.53794e-92 HMM-Q07551-FALSE_POSITIVE-3.9e-14 BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 BLAST-P32872-FALSE_POSITIVE-4.71397e-86 HMM-P00331-FALSE_POSITIVE-7.7e-14 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 BLAST-P47771-FALSE_POSITIVE-2.41892e-85 HMM-P00330-FALSE_POSITIVE-7.4e-13 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 BLAST-P54114-FALSE_POSITIVE-9.99172e-85 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 HMM-P38113-FALSE_POSITIVE-1.3e-12 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 HMM-P07246-FALSE_POSITIVE-2.7e-12 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-Q07786-FALSE_POSITIVE-8.5e-11 HMM-Q12458-FALSE_POSITIVE-2.3e-81 HMM-P35497-FALSE_POSITIVE-8.9e-11 HMM-P38715-FALSE_POSITIVE-7.3e-68 HMM-Q07993-FALSE_POSITIVE-1.3e-10 HMM-P38115-FALSE_POSITIVE-1.5e-53 HMM-P32771-FALSE_POSITIVE-2e-09 HMM-Q04894-TRUE_POSITIVE-1.4e-49 HMM-P39713-FALSE_POSITIVE-1.8e-07 HMM-P25377-TRUE_POSITIVE-1e-43 HMM-P39714-FALSE_POSITIVE-1.1e-06 HMM-P47137-FALSE_POSITIVE-5.6e-23 HMM-Q6B208-FALSE_POSITIVE-1.4e-06 HMM-Q07551-FALSE_POSITIVE-3.9e-14 HMM-P00331-FALSE_POSITIVE-7.7e-14 MARIBOES-1.1.1.265-RXN-reactionStatus=TRUE_NEGATIVE HMM-P00330-FALSE_POSITIVE-7.4e-13 HMM-P38113-FALSE_POSITIVE-1.3e-12 HMM-P07246-FALSE_POSITIVE-2.7e-12 HMM-Q07786-FALSE_POSITIVE-8.5e-11 HMM-P35497-FALSE_POSITIVE-8.9e-11 HMM-Q07993-FALSE_POSITIVE-1.3e-10 HMM-P32771-FALSE_POSITIVE-2e-09 HMM-P39713-FALSE_POSITIVE-1.8e-07 HMM-P39714-FALSE_POSITIVE-1.1e-06 HMM-Q6B208-FALSE_POSITIVE-1.4e-06

MARIBOES-1.1.1.265-RXN-reactionStatus=TRUE_NEGATIVE

2-phenylethanol phenylacetate 4α-hydroxy-tetrahydrobiopterin

RXN-7908-reactionStatus=TRUE_POSITIVE List of predictions: HMM-P38744-TRUE_POSITIVE-7.3e-12

PHENYLALANINE-4-MONOOXYGENASE-RXN-reactionStatus=FALSE_NEGATIVE dihydrobiopterin PHENYLALANINE-4-MONOOXYGENASE-RXN-reactionStatus=FALSE_NEGATIVE

RXN-7909-reactionStatus=FALSE_NEGATIVE

tetrahydrobiopterin

PHENYLALANINE-4-MONOOXYGENASE-RXN-reactionStatus=FALSE_NEGATIVE

L-tyrosine

Pathway ID: PHENYLALANINE-DEG-Saccharomyces cerevisiae D-glyceraldehyde-3-phosphate pyruvate

DXS-RXN-reactionStatus=FALSE_NEGATIVE DXS-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: List of predictions: List of predictions: List of predictions: HMM-P32473-FALSE_POSITIVE-4.6e-05 HMM-P32473-FALSE_POSITIVE-4.6e-05 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P00175-TRUE_POSITIVE-5.46824e-166 BLAST-P00175-TRUE_POSITIVE-5.46824e-166 HMM-P23254-FALSE_POSITIVE-0.00024 HMM-P23254-FALSE_POSITIVE-0.00024 HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-P33315-FALSE_POSITIVE-0.00034 HMM-P33315-FALSE_POSITIVE-0.00034 HMM-P16387-FALSE_POSITIVE-6.6e-10 HMM-Q07540-FALSE_POSITIVE-8.6e-10 HMM-Q07540-FALSE_POSITIVE-8.6e-10

1-deoxy-D-xylulose 5-phosphate acetyl-CoA L-lactate

DXPREDISOM-RXN-reactionStatus=FALSE_NEGATIVE

2-C-methyl-D-erythritol-4-phosphate

2.7.7.60-RXN-reactionStatus=FALSE_NEGATIVE

4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol

2.7.1.148-RXN-reactionStatus=FALSE_NEGATIVE

2-phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol

RXN0-302-reactionStatus=FALSE_NEGATIVE

2-C-methyl-D-erythritol-2,4-cyclodiphosphate

RXN0-882-reactionStatus=FALSE_NEGATIVE

1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate

ISPH2-RXN-reactionStatus=FALSE_NEGATIVE

RXN0-884-reactionStatus=FALSE_NEGATIVE isopentenyl diphosphate

IPPISOM-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P15496-TRUE_POSITIVE-1.03436e-70 HMM-P15496-TRUE_POSITIVE-7.1e-79 HMM-P00175-FALSE_POSITIVE-3.2e-06

GPPSYN-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P08524-TRUE_POSITIVE-7.66706e-158 BLAST-Q12051-FALSE_POSITIVE-1.75076e-66 dimethylallyl diphosphate HMM-P08524-TRUE_POSITIVE-2.7e-237 HMM-Q12051-FALSE_POSITIVE-5.5e-61 HMM-P18900-FALSE_POSITIVE-2.3e-12

GPPSYN-RXN-reactionStatus=TRUE_POSITIVE FPPSYN-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P08524-TRUE_POSITIVE-7.66706e-158 BLAST-P08524-TRUE_POSITIVE-7.66706e-158 BLAST-Q12051-FALSE_POSITIVE-1.75076e-66 BLAST-Q12051-FALSE_POSITIVE-1.75076e-66 HMM-P08524-TRUE_POSITIVE-2.7e-237 HMM-P08524-TRUE_POSITIVE-2.7e-237 HMM-Q12051-FALSE_POSITIVE-5.5e-61 HMM-Q12051-FALSE_POSITIVE-5.5e-61 HMM-P18900-FALSE_POSITIVE-2.3e-12 HMM-P18900-FALSE_POSITIVE-3.2e-12

geranyl-diphosphate

FPPSYN-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P08524-TRUE_POSITIVE-7.66706e-158 BLAST-Q12051-FALSE_POSITIVE-1.75076e-66 HMM-P08524-TRUE_POSITIVE-2.7e-237 HMM-Q12051-FALSE_POSITIVE-5.5e-61 HMM-P18900-FALSE_POSITIVE-3.2e-12

all-trans-farnesyl diphosphate

FARNESYLTRANSTRANSFERASE-RXN-reactionStatus=TRUE_POSITIVE RXN0-5180-reactionStatus=FALSE_NEGATIVE List of predictions: List of predictions: BLAST-Q12051-TRUE_POSITIVE-1.75076e-66 HMM-P35196-FALSE_POSITIVE-6.9e-60 HMM-Q12051-TRUE_POSITIVE-5.5e-61 HMM-Q03175-FALSE_POSITIVE-1.1e-39 HMM-P18900-FALSE_POSITIVE-2.5e-07 HMM-P08524-FALSE_POSITIVE-0.00019

2-cis,6-trans,10-trans-geranylgeranyl diphosphate all-trans-geranyl-geranyl diphosphate

RXN-8993-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-P35196-FALSE_POSITIVE-6.9e-60 RXN-8813-reactionStatus=POSSIBLE_NEGATIVE HMM-Q03175-FALSE_POSITIVE-1.1e-39

di-trans,poly-cis-pentaprenyl diphosphate geranylfarnesyl diphosphate

RXN-8994-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-P35196-FALSE_POSITIVE-6.9e-60 TRANS-PENTAPRENYLTRANSFERASE-RXN-reactionStatus=POSSIBLE_NEGATIVE HMM-Q03175-FALSE_POSITIVE-1.1e-39

di-trans,poly-cis-hexaprenyl diphosphate all-trans-hexaprenyl diphosphate

RXN-8995-reactionStatus=FALSE_NEGATIVE TRANS-HEXAPRENYLTRANSTRANSFERASE-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: List of predictions: HMM-P35196-FALSE_POSITIVE-6.9e-60 HMM-P18900-FALSE_POSITIVE-2.2e-08 HMM-Q03175-FALSE_POSITIVE-1.1e-39

di-trans,poly-cis-heptaprenyl diphosphate all-trans-heptaprenyl diphosphate

RXN-8996-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-P35196-FALSE_POSITIVE-6.9e-60 RXN-8992-reactionStatus=POSSIBLE_NEGATIVE HMM-Q03175-FALSE_POSITIVE-1.1e-39

di-trans,poly-cis-octaprenyl diphosphate all-trans-octaprenyl diphosphate

RXN-8997-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-P35196-FALSE_POSITIVE-6.9e-60 TRANS-OCTAPRENYLTRANSTRANSFERASE-RXN-reactionStatus=POSSIBLE_NEGATIVE HMM-Q03175-FALSE_POSITIVE-1.1e-39

di-trans,poly-cis-nonaprenyl diphosphate all-trans-nonaprenyl diphosphate

RXN-8998-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-P35196-FALSE_POSITIVE-6.9e-60 RXN-9106-reactionStatus=TRUE_NEGATIVE HMM-Q03175-FALSE_POSITIVE-1.1e-39

di-trans,poly-cis-decaprenyl diphosphate all-trans-decaprenyl diphosphate

RXN-8999-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-P35196-FALSE_POSITIVE-6.9e-60 RXN-9138-reactionStatus=TRUE_NEGATIVE HMM-Q03175-FALSE_POSITIVE-1.1e-39

di-trans,poly-cis-undecaprenyl diphosphate all-trans-undecaprenyl diphosphate

RXN-9139-reactionStatus=TRUE_NEGATIVE

all-trans-dodecaprenyl diphosphate

RXN-9364-reactionStatus=TRUE_NEGATIVE

all-trans-tridecaprenyl diphosphate

Pathway ID: Polyprenyl-Biosynthesis-Saccharomyces cerevisiae L-proline

RXN-821-reactionStatus=FALSE_NEGATIVE

RXN-7181-reactionStatus=TRUE_POSITIVE List of predictions: HMM-P09368-TRUE_POSITIVE-6.6e-05

(S)-1-pyrroline-5-carboxylate

PYRROLINECARBDEHYDROG-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P07275-TRUE_POSITIVE-3.03652e-156 BLAST-P40047-FALSE_POSITIVE-1.02785e-71 BLAST-P46367-FALSE_POSITIVE-7.60239e-68 BLAST-P47771-FALSE_POSITIVE-7.73032e-68 BLAST-P54114-FALSE_POSITIVE-5.97022e-67 BLAST-A9LRZ7-FALSE_POSITIVE-2.49413e-64 BLAST-P54115-FALSE_POSITIVE-2.49413e-64 BLAST-P32872-FALSE_POSITIVE-5.98755e-57 BLAST-P38067-FALSE_POSITIVE-8.30958e-49 HMM-P07275-TRUE_POSITIVE-7e-243 HMM-P40047-FALSE_POSITIVE-5.6e-72 HMM-P46367-FALSE_POSITIVE-1.5e-71 HMM-P54114-FALSE_POSITIVE-2.7e-62 HMM-P54115-FALSE_POSITIVE-4.9e-62 HMM-A9LRZ7-FALSE_POSITIVE-4.9e-62 HMM-P47771-FALSE_POSITIVE-8.8e-61 HMM-P32872-FALSE_POSITIVE-3.3e-39 HMM-P38067-FALSE_POSITIVE-3.5e-13 HMM-P38694-FALSE_POSITIVE-1.1e-11 HMM-Q04458-FALSE_POSITIVE-2.2e-07 HMM-P22281-FALSE_POSITIVE-9.3e-05

RXN-7183-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P07275-TRUE_POSITIVE-5.8687e-174 BLAST-P15380-TRUE_POSITIVE-2.51302e-131 BLAST-P53388-FALSE_POSITIVE-3.00927e-85 BLAST-P32487-FALSE_POSITIVE-1.1003e-73 BLAST-P40047-FALSE_POSITIVE-5.04385e-73 BLAST-P04817-FALSE_POSITIVE-1.04688e-72 BLAST-P38090-FALSE_POSITIVE-1.72759e-71 BLAST-P46367-FALSE_POSITIVE-2.38238e-70 BLAST-P47771-FALSE_POSITIVE-2.72343e-69 BLAST-P54114-FALSE_POSITIVE-4.92487e-69 BLAST-P38971-FALSE_POSITIVE-8.16708e-66 BLAST-A9LRZ7-FALSE_POSITIVE-4.84899e-65 BLAST-P54115-FALSE_POSITIVE-4.84899e-65 BLAST-P06775-FALSE_POSITIVE-3.54879e-63 BLAST-P19145-FALSE_POSITIVE-8.52736e-61 BLAST-P32872-FALSE_POSITIVE-1.84636e-57 BLAST-P25376-FALSE_POSITIVE-4.20301e-55 BLAST-P48813-FALSE_POSITIVE-1.73662e-53 BLAST-P43548-FALSE_POSITIVE-2.77417e-49 BLAST-P38067-FALSE_POSITIVE-8.30958e-49 BLAST-Q12372-FALSE_POSITIVE-3.97261e-48 BLAST-P38967-FALSE_POSITIVE-1.48461e-47 BLAST-P41815-FALSE_POSITIVE-4.35574e-47 BLAST-Q08986-FALSE_POSITIVE-9.15306e-47 BLAST-P38084-FALSE_POSITIVE-8.3528e-46 BLAST-P38694-FALSE_POSITIVE-2.63344e-41 BLAST-P38085-FALSE_POSITIVE-1.67244e-39 HMM-P07275-TRUE_POSITIVE-5.7e-257 HMM-P40047-FALSE_POSITIVE-1e-69 HMM-P46367-FALSE_POSITIVE-2.3e-64 HMM-P54115-FALSE_POSITIVE-1.3e-53 HMM-A9LRZ7-FALSE_POSITIVE-1.3e-53 HMM-P47771-FALSE_POSITIVE-5e-53 HMM-P54114-FALSE_POSITIVE-9.2e-52 HMM-P32872-FALSE_POSITIVE-3.3e-27 HMM-P38067-FALSE_POSITIVE-6.1e-15 HMM-P38694-FALSE_POSITIVE-4e-14 HMM-P27476-FALSE_POSITIVE-3.1e-09 HMM-Q04458-FALSE_POSITIVE-8.8e-09 HMM-P32588-FALSE_POSITIVE-3e-06 HMM-Q99383-FALSE_POSITIVE-3.8e-06 HMM-P04147-FALSE_POSITIVE-9.4e-06 HMM-P22281-FALSE_POSITIVE-2.7e-05 HMM-P25555-FALSE_POSITIVE-0.00061

L-glutamate

MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.3.1.36-RXN-reactionStatus=TRUE_NEGATIVE HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P38891-TRUE_POSITIVE-7.5e-157

2-oxoglutarate N-acetyl-L-glutamate

Pathway ID: PROLINE-DEG-Saccharomyces cerevisiae malate acetate pyruvate

L-LACTATE-DEHYDROGENASE-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE PYRUFLAVREDUCT-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: DLACTDEHYDROGNAD-RXN-reactionStatus=FALSE_NEGATIVE HMM-P17505-FALSE_POSITIVE-9.5e-12 List of predictions: MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE PYRUVFORMLY-RXN-reactionStatus=FALSE_NEGATIVE HMM-Q6Q5N4-FALSE_POSITIVE-2.2e-11 HMM-P40054-FALSE_POSITIVE-4.4e-19 List of predictions: List of predictions: MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE FUMHYDR-RXN-reactionStatus=TRUE_POSITIVE HMM-P32419-FALSE_POSITIVE-3.2e-09 HMM-A0SXJ4-FALSE_POSITIVE-3e-18 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 PYRUVDEH-RXN-reactionStatus=TRUE_NEGATIVE List of predictions: List of predictions: HMM-P22133-FALSE_POSITIVE-1.7e-07 HMM-P40510-FALSE_POSITIVE-4.8e-18 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P00175-TRUE_POSITIVE-5.46824e-166 BLAST-P08417-TRUE_POSITIVE-0 PYRUVFORMLY-RXN-reactionStatus=FALSE_NEGATIVE PYRUFLAVREDUCT-RXN-reactionStatus=FALSE_NEGATIVE HMM-P53839-FALSE_POSITIVE-1.9e-17 BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE HMM-P00175-TRUE_POSITIVE-1e-46 HMM-P08417-TRUE_POSITIVE-0 HMM-Q08911-FALSE_POSITIVE-2.3e-10 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 List of predictions: MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE HMM-Q07540-FALSE_POSITIVE-9.9e-09 HMM-Q08987-FALSE_POSITIVE-4.1e-10 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 List of predictions: HMM-Q02961-FALSE_POSITIVE-3.3e-05 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P32473-FALSE_POSITIVE-1.1e-55 BLAST-P00175-TRUE_POSITIVE-5.46824e-166 HMM-P53100-FALSE_POSITIVE-0.00015 HMM-P38137-FALSE_POSITIVE-2.9e-09 HMM-P38137-FALSE_POSITIVE-2.9e-09 HMM-P16387-FALSE_POSITIVE-4.8e-11 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-Q07540-FALSE_POSITIVE-9.9e-09

RXN-6161-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P06169-FALSE_POSITIVE-0 BLAST-P16467-FALSE_POSITIVE-0 BLAST-P26263-FALSE_POSITIVE-0 BLAST-Q07471-FALSE_POSITIVE-0 BLAST-Q06408-FALSE_POSITIVE-1.4799e-90 BLAST-P32896-TRUE_POSITIVE-2.06555e-74 BLAST-P87013-FALSE_POSITIVE-2.02268e-60 HMM-P06169-FALSE_POSITIVE-0 HMM-P16467-FALSE_POSITIVE-0 fumarate ACETATEKIN-RXN-reactionStatus=FALSE_NEGATIVE acetyl-CoA L-lactate formate CO2 HMM-P26263-FALSE_POSITIVE-0 D-lactate HMM-Q07471-FALSE_POSITIVE-4.4e-222 HMM-Q06408-FALSE_POSITIVE-2.3e-95 HMM-Q12017-FALSE_POSITIVE-1.7e-13 HMM-P07342-FALSE_POSITIVE-3.4e-10 HMM-P39994-FALSE_POSITIVE-2.3e-09 HMM-Q45U28-FALSE_POSITIVE-3.8e-06 HMM-P53238-FALSE_POSITIVE-4.3e-06 HMM-Q04004-FALSE_POSITIVE-3.2e-05 HMM-P25040-FALSE_POSITIVE-0.00017 HMM-Q04773-FALSE_POSITIVE-0.00034

LACCOA-RXN-reactionStatus=TRUE_NEGATIVE

MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE

MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-Q66RJ0-FALSE_POSITIVE-0 R601-RXN-reactionStatus=TRUE_NEGATIVE PHOSACETYLTRANS-RXN-reactionStatus=FALSE_NEGATIVE ACETALD-DEHYDROG-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P52910-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-2.9e-09

succinate acetylphosphate acetaldehyde D-lactoyl-CoA

ALCOHOL-DEHYDROG-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.1.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: MARIBOES-1.1.1.1-RXN-reactionStatus=TRUE_POSITIVE BLAST-P38113-TRUE_POSITIVE-0 List of predictions: BLAST-P07246-TRUE_POSITIVE-1.19444e-169 BLAST-P38113-TRUE_POSITIVE-0 BLAST-P00331-TRUE_POSITIVE-2.2163e-166 BLAST-P07246-TRUE_POSITIVE-1.19444e-169 BLAST-P00330-TRUE_POSITIVE-3.09529e-165 BLAST-P00331-TRUE_POSITIVE-2.2163e-166 BLAST-P10127-TRUE_POSITIVE-3.11897e-131 BLAST-P00330-TRUE_POSITIVE-3.09529e-165 BLAST-P32771-TRUE_POSITIVE-1.62685e-123 BLAST-P10127-TRUE_POSITIVE-3.11897e-131 BLAST-Q04018-FALSE_POSITIVE-2.98645e-81 BLAST-P32771-TRUE_POSITIVE-1.62685e-123 HMM-P32771-TRUE_POSITIVE-1e-121 BLAST-Q04018-FALSE_POSITIVE-2.98645e-81 HMM-P00331-TRUE_POSITIVE-3.2e-112 HMM-P32771-TRUE_POSITIVE-1e-121 HMM-P00330-TRUE_POSITIVE-6.9e-111 HMM-P00331-TRUE_POSITIVE-3.2e-112 HMM-P07246-TRUE_POSITIVE-4.8e-110 HMM-P00330-TRUE_POSITIVE-6.9e-111 HMM-P38113-TRUE_POSITIVE-1.7e-106 HMM-P07246-TRUE_POSITIVE-4.8e-110 HMM-Q07993-FALSE_POSITIVE-4.5e-26 HMM-P38113-TRUE_POSITIVE-1.7e-106 HMM-Q04894-FALSE_POSITIVE-2.9e-23 HMM-Q07993-FALSE_POSITIVE-4.5e-26 HMM-P35497-FALSE_POSITIVE-9.5e-21 HMM-Q04894-FALSE_POSITIVE-2.9e-23 HMM-Q07786-FALSE_POSITIVE-9.8e-21 HMM-P35497-FALSE_POSITIVE-9.5e-21 HMM-P25377-FALSE_POSITIVE-4.1e-15 HMM-Q07786-FALSE_POSITIVE-9.8e-21 HMM-P39713-FALSE_POSITIVE-6.6e-07 HMM-P25377-FALSE_POSITIVE-4.1e-15 HMM-Q6B208-FALSE_POSITIVE-9.2e-05 HMM-P39713-FALSE_POSITIVE-6.6e-07 RXN0-268-reactionStatus=TRUE_NEGATIVE HMM-P38230-FALSE_POSITIVE-0.0001 HMM-Q6B208-FALSE_POSITIVE-9.2e-05 HMM-P39714-FALSE_POSITIVE-0.00016 HMM-P38230-FALSE_POSITIVE-0.0001 MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE HMM-P39714-FALSE_POSITIVE-0.00016

MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-P32771-FALSE_POSITIVE-3.01743e-85 List of predictions: MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE LACTOYL-COA-DEHYDRATASE-RXN-reactionStatus=TRUE_NEGATIVE BLAST-P52910-TRUE_POSITIVE-0 BLAST-P38715-FALSE_POSITIVE-5.93767e-64 BLAST-P32771-FALSE_POSITIVE-3.01743e-85 BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 BLAST-P38715-FALSE_POSITIVE-5.93767e-64 HMM-P52910-TRUE_POSITIVE-0 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 HMM-Q01574-TRUE_POSITIVE-0 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 HMM-Q66RJ0-FALSE_POSITIVE-0 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 HMM-P38137-FALSE_POSITIVE-2.9e-09 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 HMM-P14065-FALSE_POSITIVE-1.2e-84 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 HMM-Q12458-FALSE_POSITIVE-2.3e-81 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-P38715-FALSE_POSITIVE-7.3e-68 HMM-Q12458-FALSE_POSITIVE-2.3e-81 HMM-P38115-FALSE_POSITIVE-1.5e-53 HMM-P38715-FALSE_POSITIVE-7.3e-68 HMM-Q04894-TRUE_POSITIVE-1.4e-49 HMM-P38115-FALSE_POSITIVE-1.5e-53 HMM-P25377-TRUE_POSITIVE-1e-43 HMM-Q04894-TRUE_POSITIVE-1.4e-49 HMM-P47137-FALSE_POSITIVE-5.6e-23 HMM-P25377-TRUE_POSITIVE-1e-43 HMM-Q07551-FALSE_POSITIVE-5e-14 HMM-P47137-FALSE_POSITIVE-5.6e-23 HMM-P00331-FALSE_POSITIVE-7.6e-12 HMM-Q07551-FALSE_POSITIVE-5e-14 HMM-P00330-FALSE_POSITIVE-1.9e-10 HMM-P00331-FALSE_POSITIVE-7.6e-12 HMM-P38113-FALSE_POSITIVE-3e-10 HMM-P00330-FALSE_POSITIVE-1.9e-10 HMM-P07246-FALSE_POSITIVE-5.6e-10 HMM-P38113-FALSE_POSITIVE-3e-10 HMM-Q07786-FALSE_POSITIVE-2.8e-09 HMM-P07246-FALSE_POSITIVE-5.6e-10 HMM-P35497-FALSE_POSITIVE-2.9e-09 HMM-Q07786-FALSE_POSITIVE-2.8e-09 HMM-Q07993-FALSE_POSITIVE-4e-09 HMM-P35497-FALSE_POSITIVE-2.9e-09 HMM-P32771-FALSE_POSITIVE-4.4e-08 HMM-Q07993-FALSE_POSITIVE-4e-09 HMM-P39713-FALSE_POSITIVE-5.9e-06 HMM-P32771-FALSE_POSITIVE-4.4e-08 HMM-Q6B208-FALSE_POSITIVE-1.6e-05 HMM-P39713-FALSE_POSITIVE-5.9e-06 HMM-P39714-FALSE_POSITIVE-1.6e-05 HMM-Q6B208-FALSE_POSITIVE-1.6e-05 HMM-P39714-FALSE_POSITIVE-1.6e-05

MARIBOES-1.1.1.265-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-1.1.1.265-RXN-reactionStatus=TRUE_NEGATIVE

MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P32771-FALSE_POSITIVE-3.01743e-85 BLAST-P38715-FALSE_POSITIVE-5.93767e-64 BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-Q12458-FALSE_POSITIVE-2.3e-81 HMM-P38715-FALSE_POSITIVE-7.3e-68 LACCOA-RXN-reactionStatus=TRUE_NEGATIVE LACCOA-RXN-reactionStatus=TRUE_NEGATIVE HMM-P38115-FALSE_POSITIVE-1.5e-53 MALATE-DEH-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE HMM-Q04894-TRUE_POSITIVE-1.4e-49 List of predictions: HMM-P25377-TRUE_POSITIVE-1e-43 BLAST-Q6Q5N4-POSSIBLE_POSITIVE-2.47512e-87 MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE HMM-P47137-FALSE_POSITIVE-5.6e-23 BLAST-P17505-TRUE_POSITIVE-4.30247e-85 HMM-Q07551-FALSE_POSITIVE-5e-14 List of predictions: List of predictions: BLAST-P32419-TRUE_POSITIVE-1.42548e-62 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 succinyl-CoA HMM-P00331-FALSE_POSITIVE-7.6e-12 BLAST-P22133-TRUE_POSITIVE-2.01854e-58 ethanol acrylyl-CoA HMM-P00330-FALSE_POSITIVE-1.9e-10 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 HMM-P17505-TRUE_POSITIVE-1.1e-113 BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P38113-FALSE_POSITIVE-3e-10 HMM-Q6Q5N4-POSSIBLE_POSITIVE-3.4e-112 HMM-P07246-FALSE_POSITIVE-5.6e-10 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P32419-TRUE_POSITIVE-1.7e-65 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q07786-FALSE_POSITIVE-2.8e-09 HMM-P22133-TRUE_POSITIVE-6.9e-51 HMM-P35497-FALSE_POSITIVE-2.9e-09 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q07993-FALSE_POSITIVE-4e-09 HMM-P38137-FALSE_POSITIVE-2.9e-09 HMM-P38137-FALSE_POSITIVE-2.9e-09 HMM-P32771-FALSE_POSITIVE-4.4e-08 HMM-P39713-FALSE_POSITIVE-5.9e-06 HMM-Q6B208-FALSE_POSITIVE-1.6e-05 HMM-P39714-FALSE_POSITIVE-1.6e-05

MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P00175-TRUE_POSITIVE-5.46824e-166 HMM-P00175-TRUE_POSITIVE-1e-46 HMM-Q07540-FALSE_POSITIVE-9.9e-09

MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 METHYLMALONYL-COA-MUT-RXN-reactionStatus=FALSE_NEGATIVE RXN-8568-reactionStatus=FALSE_NEGATIVE BLAST-Q01574-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-2.9e-09 HMM-P38137-FALSE_POSITIVE-2.9e-09

(R)-methylmalonyl-CoA propionyl-CoA acrylate

PROPIONATE-COA-TRANSFERASE-RXN-reactionStatus=FALSE_NEGATIVE

MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE LACCOA-RXN-reactionStatus=TRUE_NEGATIVE

MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: List of predictions: List of predictions: BLAST-Q66RJ0-FALSE_POSITIVE-0 MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P52910-TRUE_POSITIVE-0 List of predictions: METHYLMALONYL-COA-EPIM-RXN-reactionStatus=FALSE_NEGATIVE HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P32473-FALSE_POSITIVE-1.1e-55 BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 HMM-P16387-FALSE_POSITIVE-4.8e-11 HMM-P16387-FALSE_POSITIVE-4.8e-11 HMM-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-2.9e-09 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-2.9e-09

(S)-methylmalonyl-CoA 2-oxobutanoate propionate

2.1.3.1-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P32327-FALSE_POSITIVE-5.78971e-61 HMM-P32327-FALSE_POSITIVE-1.2e-09 HMM-P11154-FALSE_POSITIVE-1.5e-09

oxaloacetate

MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P38891-TRUE_POSITIVE-7.5e-157

L-aspartate

Pathway ID: Pyruvate-Degradation-Saccharomyces cerevisiae L-threonine

THREODEHYD-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-Q07993-FALSE_POSITIVE-1.2e-20 HMM-P35497-FALSE_POSITIVE-3.1e-19 HMM-Q07786-FALSE_POSITIVE-6.5e-19 THREDEHYD-RXN-reactionStatus=TRUE_POSITIVE HMM-P39714-FALSE_POSITIVE-5.8e-16 List of predictions: HMM-Q6B208-FALSE_POSITIVE-8e-16 BLAST-P00927-TRUE_POSITIVE-0 THREONINE-ALDOLASE-RXN-reactionStatus=TRUE_POSITIVE HMM-P32771-FALSE_POSITIVE-7e-14 BLAST-P36007-FALSE_POSITIVE-4.80041e-50 List of predictions: HMM-P39713-FALSE_POSITIVE-1.7e-13 HMM-P00927-TRUE_POSITIVE-1.1e-301 BLAST-P37303-TRUE_POSITIVE-0 HMM-P07246-FALSE_POSITIVE-3.9e-13 HMM-P36007-FALSE_POSITIVE-3.3e-85 HMM-P37303-TRUE_POSITIVE-1.7e-210 HMM-P38113-FALSE_POSITIVE-5e-13 HMM-P17324-FALSE_POSITIVE-1.2e-07 HMM-P00331-FALSE_POSITIVE-1e-12 HMM-P25379-TRUE_POSITIVE-1.7e-07 HMM-P00330-FALSE_POSITIVE-1.9e-12 HMM-Q04894-FALSE_POSITIVE-3.1e-11 HMM-P25377-FALSE_POSITIVE-1.3e-09 HMM-P38230-FALSE_POSITIVE-1.6e-06

THREONINE-ALDOLASE-RXN-reactionStatus=TRUE_POSITIVE List of predictions: 2-amino-3-oxobutanoate BLAST-P37303-TRUE_POSITIVE-0 2-oxobutanoate acetaldehyde pyruvate HMM-P37303-TRUE_POSITIVE-1.7e-210

MARIBOES-1.1.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P38113-TRUE_POSITIVE-0 BLAST-P38113-TRUE_POSITIVE-0 BLAST-P07246-TRUE_POSITIVE-1.19444e-169 BLAST-P07246-TRUE_POSITIVE-1.19444e-169 BLAST-P00331-TRUE_POSITIVE-2.2163e-166 BLAST-P00331-TRUE_POSITIVE-2.2163e-166 BLAST-P00330-TRUE_POSITIVE-3.09529e-165 BLAST-P00330-TRUE_POSITIVE-3.09529e-165 BLAST-P10127-TRUE_POSITIVE-3.11897e-131 BLAST-P10127-TRUE_POSITIVE-3.11897e-131 BLAST-P32771-TRUE_POSITIVE-1.62685e-123 BLAST-P32771-TRUE_POSITIVE-1.62685e-123 BLAST-Q04018-FALSE_POSITIVE-2.98645e-81 BLAST-Q04018-FALSE_POSITIVE-2.98645e-81 HMM-P32771-TRUE_POSITIVE-1e-121 HMM-P32771-TRUE_POSITIVE-1e-121 HMM-P00331-TRUE_POSITIVE-3.2e-112 HMM-P00331-TRUE_POSITIVE-3.2e-112 HMM-P00330-TRUE_POSITIVE-6.9e-111 HMM-P00330-TRUE_POSITIVE-6.9e-111 HMM-P07246-TRUE_POSITIVE-4.8e-110 HMM-P07246-TRUE_POSITIVE-4.8e-110 HMM-P38113-TRUE_POSITIVE-1.7e-106 HMM-P38113-TRUE_POSITIVE-1.7e-106 HMM-Q07993-FALSE_POSITIVE-4.5e-26 HMM-Q07993-FALSE_POSITIVE-4.5e-26 HMM-Q04894-FALSE_POSITIVE-2.9e-23 HMM-Q04894-FALSE_POSITIVE-2.9e-23 HMM-P35497-FALSE_POSITIVE-9.5e-21 HMM-P35497-FALSE_POSITIVE-9.5e-21 HMM-Q07786-FALSE_POSITIVE-9.8e-21 HMM-Q07786-FALSE_POSITIVE-9.8e-21 HMM-P25377-FALSE_POSITIVE-4.1e-15 HMM-P25377-FALSE_POSITIVE-4.1e-15 HMM-P39713-FALSE_POSITIVE-5.4e-08 HMM-P39713-FALSE_POSITIVE-5.4e-08 HMM-Q6B208-FALSE_POSITIVE-1.2e-06 HMM-Q6B208-FALSE_POSITIVE-1.2e-06 HMM-P38230-FALSE_POSITIVE-1.4e-06 HMM-P38230-FALSE_POSITIVE-1.4e-06 HMM-P39714-FALSE_POSITIVE-2.5e-06 HMM-P39714-FALSE_POSITIVE-2.5e-06

KETOBUTFORMLY-RXN-reactionStatus=TRUE_NEGATIVE AKBLIG-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.2.3-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: List of predictions: List of predictions: MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: List of predictions: List of predictions: List of predictions: HMM-P40970-FALSE_POSITIVE-2e-45 BLAST-P00175-TRUE_POSITIVE-5.46824e-166 BLAST-P00175-TRUE_POSITIVE-5.46824e-166 List of predictions: BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P32771-FALSE_POSITIVE-3.01743e-85 BLAST-P32771-FALSE_POSITIVE-3.01743e-85 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 THREOSPON-RXN-reactionStatus=TRUE_NEGATIVE HMM-P09950-FALSE_POSITIVE-2.8e-45 ACETALD-DEHYDROG-RXN-reactionStatus=FALSE_NEGATIVE HMM-P00175-TRUE_POSITIVE-1e-46 HMM-P00175-TRUE_POSITIVE-1e-46 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 HMM-P32473-FALSE_POSITIVE-1.1e-55 BLAST-P38715-FALSE_POSITIVE-5.93767e-64 BLAST-P38715-FALSE_POSITIVE-5.93767e-64 HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-Q66RF3-FALSE_POSITIVE-4.6e-44 HMM-Q07540-FALSE_POSITIVE-2.1e-10 HMM-Q07540-FALSE_POSITIVE-2.1e-10 HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P16387-FALSE_POSITIVE-4e-12 BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 HMM-P16387-FALSE_POSITIVE-4e-12 HMM-P25045-FALSE_POSITIVE-3.7e-09 HMM-P16387-FALSE_POSITIVE-4e-12 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-Q12458-FALSE_POSITIVE-2.3e-81 HMM-Q12458-FALSE_POSITIVE-2.3e-81 HMM-P38715-FALSE_POSITIVE-7.3e-68 HMM-P38715-FALSE_POSITIVE-7.3e-68 HMM-P38115-FALSE_POSITIVE-1.5e-53 HMM-P38115-FALSE_POSITIVE-1.5e-53 HMM-Q04894-TRUE_POSITIVE-1.4e-49 HMM-Q04894-TRUE_POSITIVE-1.4e-49 HMM-P25377-TRUE_POSITIVE-1e-43 HMM-P25377-TRUE_POSITIVE-1e-43 HMM-P47137-FALSE_POSITIVE-5.6e-23 HMM-P47137-FALSE_POSITIVE-5.6e-23 HMM-Q07551-FALSE_POSITIVE-5.6e-15 HMM-Q07551-FALSE_POSITIVE-5.6e-15 HMM-P00331-FALSE_POSITIVE-7.6e-12 HMM-P00331-FALSE_POSITIVE-7.6e-12 HMM-Q07786-FALSE_POSITIVE-9e-11 HMM-Q07786-FALSE_POSITIVE-9e-11 HMM-P35497-FALSE_POSITIVE-9.4e-11 HMM-P35497-FALSE_POSITIVE-9.4e-11 HMM-Q07993-FALSE_POSITIVE-1.4e-10 HMM-Q07993-FALSE_POSITIVE-1.4e-10 HMM-P00330-FALSE_POSITIVE-1.7e-10 HMM-P00330-FALSE_POSITIVE-1.7e-10 HMM-P38113-FALSE_POSITIVE-2.7e-10 HMM-P38113-FALSE_POSITIVE-2.7e-10 HMM-P07246-FALSE_POSITIVE-5e-10 HMM-P07246-FALSE_POSITIVE-5e-10 HMM-P32771-FALSE_POSITIVE-2e-09 HMM-P32771-FALSE_POSITIVE-2e-09 HMM-P39714-FALSE_POSITIVE-1.5e-06 HMM-P39714-FALSE_POSITIVE-1.5e-06 HMM-Q6B208-FALSE_POSITIVE-1.6e-06 HMM-Q6B208-FALSE_POSITIVE-1.6e-06 HMM-P39713-FALSE_POSITIVE-2.9e-06 HMM-P39713-FALSE_POSITIVE-2.9e-06

MARIBOES-1.1.1.265-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-1.1.1.265-RXN-reactionStatus=TRUE_NEGATIVE

aminoacetone glycine 2-hydroxybutyrate propionyl-CoA ethanol acetyl-CoA

MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE

MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 AMACETOXID-RXN-reactionStatus=FALSE_NEGATIVE PTAALT-RXN-reactionStatus=TRUE_NEGATIVE BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-3.3e-10 HMM-P38137-FALSE_POSITIVE-3.3e-10

MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE

MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 methylglyoxal propionyl-P acetate BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-3.3e-10 HMM-P38137-FALSE_POSITIVE-3.3e-10

MARIBOES-1.1.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P38113-TRUE_POSITIVE-0 BLAST-P07246-TRUE_POSITIVE-1.19444e-169 BLAST-P00331-TRUE_POSITIVE-2.2163e-166 BLAST-P00330-TRUE_POSITIVE-3.09529e-165 BLAST-P10127-TRUE_POSITIVE-3.11897e-131 BLAST-P32771-TRUE_POSITIVE-1.62685e-123 BLAST-Q04018-FALSE_POSITIVE-2.98645e-81 HMM-P32771-TRUE_POSITIVE-1e-121 HMM-P00331-TRUE_POSITIVE-3.2e-112 HMM-P00330-TRUE_POSITIVE-6.9e-111 MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE HMM-P07246-TRUE_POSITIVE-4.8e-110 MARIBOES-1.1.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.1.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: HMM-P38113-TRUE_POSITIVE-1.7e-106 List of predictions: List of predictions: BLAST-P32771-FALSE_POSITIVE-3.01743e-85 HMM-Q07993-FALSE_POSITIVE-4.5e-26 BLAST-P38113-TRUE_POSITIVE-0 BLAST-P38113-TRUE_POSITIVE-0 BLAST-P38715-FALSE_POSITIVE-5.93767e-64 HMM-Q04894-FALSE_POSITIVE-2.9e-23 BLAST-P07246-TRUE_POSITIVE-1.19444e-169 BLAST-P07246-TRUE_POSITIVE-1.19444e-169 BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 HMM-P35497-FALSE_POSITIVE-9.5e-21 BLAST-P00331-TRUE_POSITIVE-2.2163e-166 BLAST-P00331-TRUE_POSITIVE-2.2163e-166 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 HMM-Q07786-FALSE_POSITIVE-9.8e-21 BLAST-P00330-TRUE_POSITIVE-3.09529e-165 BLAST-P00330-TRUE_POSITIVE-3.09529e-165 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 HMM-P25377-FALSE_POSITIVE-4.1e-15 BLAST-P10127-TRUE_POSITIVE-3.11897e-131 BLAST-P10127-TRUE_POSITIVE-3.11897e-131 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 HMM-P39713-FALSE_POSITIVE-5.4e-08 BLAST-P32771-TRUE_POSITIVE-1.62685e-123 BLAST-P32771-TRUE_POSITIVE-1.62685e-123 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 HMM-Q6B208-FALSE_POSITIVE-1.2e-06 BLAST-Q04018-FALSE_POSITIVE-2.98645e-81 BLAST-Q04018-FALSE_POSITIVE-2.98645e-81 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-P38230-FALSE_POSITIVE-1.4e-06 HMM-P32771-TRUE_POSITIVE-1e-121 HMM-P32771-TRUE_POSITIVE-1e-121 HMM-Q12458-FALSE_POSITIVE-2.3e-81 HMM-P39714-FALSE_POSITIVE-2.5e-06 HMM-P00331-TRUE_POSITIVE-3.2e-112 HMM-P00331-TRUE_POSITIVE-3.2e-112 HMM-P38715-FALSE_POSITIVE-7.3e-68 HMM-P00330-TRUE_POSITIVE-6.9e-111 HMM-P00330-TRUE_POSITIVE-6.9e-111 HMM-P38115-FALSE_POSITIVE-1.5e-53 MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE HMM-P07246-TRUE_POSITIVE-4.8e-110 HMM-P07246-TRUE_POSITIVE-4.8e-110 HMM-Q04894-TRUE_POSITIVE-1.4e-49 List of predictions: HMM-P38113-TRUE_POSITIVE-1.7e-106 HMM-P38113-TRUE_POSITIVE-1.7e-106 HMM-P25377-TRUE_POSITIVE-1e-43 BLAST-P32771-FALSE_POSITIVE-3.01743e-85 HMM-Q07993-FALSE_POSITIVE-4.5e-26 HMM-Q07993-FALSE_POSITIVE-4.5e-26 HMM-P47137-FALSE_POSITIVE-5.6e-23 PROPKIN-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P38715-FALSE_POSITIVE-5.93767e-64 HMM-Q04894-FALSE_POSITIVE-2.9e-23 HMM-Q04894-FALSE_POSITIVE-2.9e-23 HMM-Q07551-FALSE_POSITIVE-5.6e-15 BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 HMM-P35497-FALSE_POSITIVE-9.5e-21 HMM-P35497-FALSE_POSITIVE-9.5e-21 HMM-P00331-FALSE_POSITIVE-7.6e-12 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 HMM-Q07786-FALSE_POSITIVE-9.8e-21 HMM-Q07786-FALSE_POSITIVE-9.8e-21 HMM-Q07786-FALSE_POSITIVE-9e-11 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 HMM-P25377-FALSE_POSITIVE-4.1e-15 HMM-P25377-FALSE_POSITIVE-4.1e-15 HMM-P35497-FALSE_POSITIVE-9.4e-11 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 HMM-P39713-FALSE_POSITIVE-5.4e-08 HMM-P39713-FALSE_POSITIVE-5.4e-08 HMM-Q07993-FALSE_POSITIVE-1.4e-10 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 HMM-Q6B208-FALSE_POSITIVE-1.2e-06 HMM-Q6B208-FALSE_POSITIVE-1.2e-06 HMM-P00330-FALSE_POSITIVE-1.7e-10 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-P38230-FALSE_POSITIVE-1.4e-06 HMM-P38230-FALSE_POSITIVE-1.4e-06 HMM-P38113-FALSE_POSITIVE-2.7e-10 HMM-Q12458-FALSE_POSITIVE-2.3e-81 HMM-P39714-FALSE_POSITIVE-2.5e-06 HMM-P39714-FALSE_POSITIVE-2.5e-06 HMM-P07246-FALSE_POSITIVE-5e-10 HMM-P38715-FALSE_POSITIVE-7.3e-68 HMM-P32771-FALSE_POSITIVE-2e-09 HMM-P38115-FALSE_POSITIVE-1.5e-53 HMM-P39714-FALSE_POSITIVE-1.5e-06 HMM-Q04894-TRUE_POSITIVE-1.4e-49 MARIBOES-1.1.1.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.1.1.4-RXN-reactionStatus=FALSE_NEGATIVE HMM-Q6B208-FALSE_POSITIVE-1.6e-06 HMM-P25377-TRUE_POSITIVE-1e-43 List of predictions: List of predictions: HMM-P39713-FALSE_POSITIVE-2.9e-06 HMM-P47137-FALSE_POSITIVE-5.6e-23 BLAST-P25337-FALSE_POSITIVE-3.96292e-40 BLAST-P25337-FALSE_POSITIVE-3.96292e-40 HMM-Q07551-FALSE_POSITIVE-5.6e-15 HMM-P25337-FALSE_POSITIVE-6e-57 HMM-P25337-FALSE_POSITIVE-6e-57 MARIBOES-1.1.1.265-RXN-reactionStatus=TRUE_NEGATIVE HMM-P00331-FALSE_POSITIVE-7.6e-12 HMM-Q07786-FALSE_POSITIVE-9e-11 HMM-P35497-FALSE_POSITIVE-9.4e-11 HMM-Q07993-FALSE_POSITIVE-1.4e-10 HMM-P00330-FALSE_POSITIVE-1.7e-10 HMM-P38113-FALSE_POSITIVE-2.7e-10 HMM-P07246-FALSE_POSITIVE-5e-10 HMM-P32771-FALSE_POSITIVE-2e-09 HMM-P39714-FALSE_POSITIVE-1.5e-06 HMM-Q6B208-FALSE_POSITIVE-1.6e-06 HMM-P39713-FALSE_POSITIVE-2.9e-06

MARIBOES-1.1.1.265-RXN-reactionStatus=TRUE_NEGATIVE

acetol L-lactaldehyde propionate

Pathway ID: THREONINE-DEG-Saccharomyces cerevisiae ADP-D-glucose GDP-α-D-glucose UDP-D-glucose α-D-glucose 6-phosphate

MARIBOES-2.7.1.1-RXN-reactionStatus=TRUE_POSITIVE RXN-761-reactionStatus=TRUE_NEGATIVE List of predictions: BLAST-P04806-TRUE_POSITIVE-0 TREHALOSE6PSYN-RXN-reactionStatus=TRUE_POSITIVE 2.4.1.36-RXN-reactionStatus=TRUE_NEGATIVE BLAST-P04807-TRUE_POSITIVE-0 List of predictions: BLAST-P17709-FALSE_POSITIVE-5.81018e-80 MARIBOES-2.7.1.1-RXN-reactionStatus=TRUE_POSITIVE BLAST-A1E5M4-FALSE_POSITIVE-0 TREHALOSE6PSYN-RXN-reactionStatus=TRUE_POSITIVE BLAST-Q04409-FALSE_POSITIVE-1.83418e-73 List of predictions: BLAST-Q00764-TRUE_POSITIVE-0 List of predictions: HMM-P04806-TRUE_POSITIVE-5.8e-218 BLAST-P04806-TRUE_POSITIVE-0 BLAST-B2KKZ0-FALSE_POSITIVE-0 BLAST-A1E5M4-FALSE_POSITIVE-0 HMM-P04807-TRUE_POSITIVE-4.4e-217 BLAST-P04807-TRUE_POSITIVE-0 BLAST-P38426-TRUE_POSITIVE-3.58759e-124 BLAST-Q00764-TRUE_POSITIVE-0 HMM-Q04409-FALSE_POSITIVE-1e-128 BLAST-P17709-FALSE_POSITIVE-5.81018e-80 BLAST-P38427-FALSE_POSITIVE-2.21186e-123 BLAST-B2KKZ0-FALSE_POSITIVE-0 HMM-P17709-FALSE_POSITIVE-7.2e-128 BLAST-Q04409-FALSE_POSITIVE-1.83418e-73 BLAST-P31688-FALSE_POSITIVE-4.13518e-120 BLAST-P38426-TRUE_POSITIVE-3.58759e-124 HMM-Q06204-TRUE_POSITIVE-1.1e-06 HMM-P04806-TRUE_POSITIVE-5.8e-218 BLAST-B5LYT2-FALSE_POSITIVE-8.59366e-78 BLAST-P38427-FALSE_POSITIVE-2.21186e-123 HMM-P04807-TRUE_POSITIVE-4.4e-217 RXN-761-reactionStatus=TRUE_NEGATIVE MARIBOES-2.7.7.37-RXN-reactionStatus=TRUE_NEGATIVE 2.4.1.36-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.7.7.37-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.7.7.37-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.7.7.37-RXN-reactionStatus=TRUE_NEGATIVE HMM-P34161-FALSE_POSITIVE-1.2e-05 BLAST-Q7LIJ9-FALSE_POSITIVE-2.6654e-58 BLAST-P31688-FALSE_POSITIVE-4.13518e-120 HMM-Q04116-FALSE_POSITIVE-3.9e-05 HMM-Q04409-FALSE_POSITIVE-1e-128 HMM-A1E5M4-FALSE_POSITIVE-0 BLAST-B5LYT2-FALSE_POSITIVE-8.59366e-78 HMM-P07269-FALSE_POSITIVE-0.00054 HMM-P17709-FALSE_POSITIVE-7.2e-128 HMM-B2KKZ0-FALSE_POSITIVE-0 BLAST-Q7LIJ9-FALSE_POSITIVE-2.6654e-58 HMM-Q06858-FALSE_POSITIVE-0.00054 HMM-Q06204-TRUE_POSITIVE-1.1e-06 HMM-Q00764-TRUE_POSITIVE-0 HMM-A1E5M4-FALSE_POSITIVE-0 HMM-P34161-FALSE_POSITIVE-1.2e-05 HMM-P38427-FALSE_POSITIVE-3.5e-102 HMM-B2KKZ0-FALSE_POSITIVE-0 HMM-Q04116-FALSE_POSITIVE-3.9e-05 HMM-P38426-TRUE_POSITIVE-1.5e-98 HMM-Q00764-TRUE_POSITIVE-0 MARIBOES-3.1.3.1-RXN-reactionStatus=TRUE_POSITIVE HMM-P07269-FALSE_POSITIVE-0.00054 HMM-P31688-FALSE_POSITIVE-4e-77 HMM-P38427-FALSE_POSITIVE-3.5e-102 List of predictions: HMM-Q06858-FALSE_POSITIVE-0.00054 HMM-B5LYT2-FALSE_POSITIVE-9.9e-05 HMM-P38426-TRUE_POSITIVE-1.5e-98 BLAST-P11491-TRUE_POSITIVE-4.33135e-102 HMM-P31688-FALSE_POSITIVE-4e-77 BLAST-Q66RD0-FALSE_POSITIVE-1.28731e-49 HMM-B5LYT2-FALSE_POSITIVE-9.9e-05 HMM-P11491-TRUE_POSITIVE-8.1e-29 HMM-Q66RD0-FALSE_POSITIVE-1.8e-28

RXN-9603-reactionStatus=TRUE_NEGATIVE guanosine-5'-diphosphate D-Glucose trehalose 6-phosphate maltose RXN-9613-reactionStatus=TRUE_NEGATIVE uridine-5'-diphosphate α-D-glucose 1-phosphate 6-alpha-D--1-4-alpha-D-Glucano--Glucan maltooligosyl-trehalose α-D-glucose

5.4.99.16-RXN-reactionStatus=FALSE_NEGATIVE TREHALOSEPHOSPHA-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P38158-FALSE_POSITIVE-5.78386e-50 BLAST-P31688-TRUE_POSITIVE-1.59598e-154 BLAST-P53341-FALSE_POSITIVE-5.93046e-50 RXN-9603-reactionStatus=TRUE_NEGATIVE BLAST-P38426-FALSE_POSITIVE-9.49375e-76 BLAST-P07265-FALSE_POSITIVE-9.00059e-50 BLAST-P38427-FALSE_POSITIVE-1.41906e-70 BLAST-P53051-FALSE_POSITIVE-6.83623e-49 RXN-4301-reactionStatus=FALSE_NEGATIVE 3.2.1.141-RXN-reactionStatus=FALSE_NEGATIVE 3.2.1.141-RXN-reactionStatus=FALSE_NEGATIVE 5.4.99.15-RXN-reactionStatus=FALSE_NEGATIVE RXN-9613-reactionStatus=TRUE_NEGATIVE BLAST-Q00764-FALSE_POSITIVE-5.30628e-68 BLAST-Q76CZ0-FALSE_POSITIVE-7.36935e-49 BLAST-B2KKZ0-FALSE_POSITIVE-7.47067e-68 BLAST-P40439-FALSE_POSITIVE-2.27641e-43 HMM-P31688-TRUE_POSITIVE-5e-123 BLAST-Q08295-FALSE_POSITIVE-2.31472e-43 BLAST-P40884-FALSE_POSITIVE-2.81401e-40

trehalose CPD-1790

Pathway ID: Trehalose-biosynthesis-Saccharomyces cerevisiae trehalose

RXN-4441-reactionStatus=POSSIBLE_NEGATIVE

RXN-4441-reactionStatus=POSSIBLE_NEGATIVE α-D-glucose 1-phosphate

ALPHAALPHA-TREHALOSE-PHOSPHORYLASE-RXN-reactionStatus=TRUE_NEGATIVE

TREHALA-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-3.1.3.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-3.1.3.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: List of predictions: BLAST-P35172-TRUE_POSITIVE-0 BLAST-P11491-TRUE_POSITIVE-4.33135e-102 BLAST-P11491-TRUE_POSITIVE-4.33135e-102 BLAST-P32356-TRUE_POSITIVE-0 ALPHAALPHA-TREHALOSE-PHOSPHORYLASE-RXN-reactionStatus=TRUE_NEGATIVE BLAST-Q66RD0-FALSE_POSITIVE-1.28731e-49 BLAST-Q66RD0-FALSE_POSITIVE-1.28731e-49 MARIBOES-2.7.7.37-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.7.7.37-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.7.7.37-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-2.7.7.37-RXN-reactionStatus=TRUE_NEGATIVE BLAST-Q05216-POSSIBLE_POSITIVE-2.25579e-99 HMM-P11491-TRUE_POSITIVE-8.1e-29 HMM-P11491-TRUE_POSITIVE-8.1e-29 BLAST-P48016-TRUE_POSITIVE-1.0205e-92 HMM-Q66RD0-FALSE_POSITIVE-1.8e-28 HMM-Q66RD0-FALSE_POSITIVE-1.8e-28 HMM-P32356-TRUE_POSITIVE-0 HMM-P35172-TRUE_POSITIVE-0 HMM-Q05216-POSSIBLE_POSITIVE-1.6e-18

trehalose 6-phosphate α-D-glucose phosphate 5.4.2.5-RXN-reactionStatus=TRUE_NEGATIVE UDP-D-glucose

MARIBOES-3.2.1.26-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-3.2.1.26-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: BLAST-P32568-FALSE_POSITIVE-0 BLAST-P32568-FALSE_POSITIVE-0 BLAST-P33302-FALSE_POSITIVE-0 BLAST-P33302-FALSE_POSITIVE-0 BLAST-P53756-FALSE_POSITIVE-0 BLAST-P53756-FALSE_POSITIVE-0 BLAST-Q04182-FALSE_POSITIVE-0 BLAST-Q04182-FALSE_POSITIVE-0 BLAST-Q02785-FALSE_POSITIVE-0 BLAST-Q02785-FALSE_POSITIVE-0 BLAST-P51533-FALSE_POSITIVE-0 BLAST-P51533-FALSE_POSITIVE-0 BLAST-Q08409-FALSE_POSITIVE-0 BLAST-Q08409-FALSE_POSITIVE-0 BLAST-P40550-FALSE_POSITIVE-0 BLAST-P40550-FALSE_POSITIVE-0 BLAST-Q07324-FALSE_POSITIVE-3.90154e-165 BLAST-Q07324-FALSE_POSITIVE-3.90154e-165 BLAST-Q65C74-FALSE_POSITIVE-2.41635e-145 BLAST-Q65C74-FALSE_POSITIVE-2.41635e-145 BLAST-P00724-TRUE_POSITIVE-8.16982e-145 BLAST-P00724-TRUE_POSITIVE-8.16982e-145 BLAST-P10596-TRUE_POSITIVE-1.8353e-144 BLAST-P10596-TRUE_POSITIVE-1.8353e-144 BLAST-P10594-TRUE_POSITIVE-2.78621e-143 BLAST-P10594-TRUE_POSITIVE-2.78621e-143 BLAST-Q06631-TRUE_POSITIVE-6.53728e-131 BLAST-Q06631-TRUE_POSITIVE-6.53728e-131 BLAST-Q02868-FALSE_POSITIVE-9.46844e-100 BLAST-Q02868-FALSE_POSITIVE-9.46844e-100 BLAST-Q02922-FALSE_POSITIVE-2.92077e-70 BLAST-Q02922-FALSE_POSITIVE-2.92077e-70 BLAST-Q08234-FALSE_POSITIVE-4.0182e-43 BLAST-Q08234-FALSE_POSITIVE-4.0182e-43 BLAST-P30606-FALSE_POSITIVE-7.60709e-42 BLAST-P30606-FALSE_POSITIVE-7.60709e-42 MARIBOES-2.7.1.1-RXN-reactionStatus=TRUE_POSITIVE BLAST-P30605-FALSE_POSITIVE-4.84918e-41 BLAST-P30605-FALSE_POSITIVE-4.84918e-41 List of predictions: BLAST-P13181-FALSE_POSITIVE-3.74508e-40 BLAST-P13181-FALSE_POSITIVE-3.74508e-40 HMM-Q06631-TRUE_POSITIVE-1.2e-160 HMM-Q06631-TRUE_POSITIVE-1.2e-160 TRE6PHYDRO-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P04806-TRUE_POSITIVE-0 HMM-Q65C74-FALSE_POSITIVE-5.5e-111 HMM-Q65C74-FALSE_POSITIVE-5.5e-111 List of predictions: BLAST-P04807-TRUE_POSITIVE-0 MARIBOES-2.7.1.1-RXN-reactionStatus=TRUE_POSITIVE HMM-P10596-TRUE_POSITIVE-4.3e-110 HMM-P10596-TRUE_POSITIVE-4.3e-110 BLAST-P40884-FALSE_POSITIVE-1.53429e-116 BLAST-P17709-FALSE_POSITIVE-5.81018e-80 List of predictions: HMM-P10594-TRUE_POSITIVE-1.4e-107 HMM-P10594-TRUE_POSITIVE-1.4e-107 BLAST-P53051-FALSE_POSITIVE-1.758e-107 BLAST-Q04409-FALSE_POSITIVE-1.83418e-73 BLAST-P04806-TRUE_POSITIVE-0 HMM-P00724-TRUE_POSITIVE-7.9e-107 HMM-P00724-TRUE_POSITIVE-7.9e-107 BLAST-Q76CZ0-FALSE_POSITIVE-3.0747e-107 HMM-P04806-TRUE_POSITIVE-5.8e-218 BLAST-P04807-TRUE_POSITIVE-0 HMM-P30605-FALSE_POSITIVE-3.3e-09 HMM-P30605-FALSE_POSITIVE-3.3e-09 BLAST-Q08295-FALSE_POSITIVE-3.54533e-105 ALDOSE-1-EPIMERASE-RXN-reactionStatus=TRUE_POSITIVE HMM-P04807-TRUE_POSITIVE-4.4e-217 BLAST-P17709-FALSE_POSITIVE-5.81018e-80 HMM-P30606-FALSE_POSITIVE-4.4e-09 HMM-P30606-FALSE_POSITIVE-4.4e-09 BLAST-P40439-FALSE_POSITIVE-4.78749e-105 List of predictions: HMM-Q04409-FALSE_POSITIVE-1e-128 BLAST-Q04409-FALSE_POSITIVE-1.83418e-73 HMM-Q12300-FALSE_POSITIVE-1e-07 HMM-Q12300-FALSE_POSITIVE-1e-07 BLAST-P53341-FALSE_POSITIVE-1.32762e-97 BLAST-P04397-TRUE_POSITIVE-0 HMM-P17709-FALSE_POSITIVE-7.2e-128 HMM-P04806-TRUE_POSITIVE-5.8e-218 HMM-P32465-FALSE_POSITIVE-1.3e-07 HMM-P32465-FALSE_POSITIVE-1.3e-07 BLAST-P38158-FALSE_POSITIVE-3.83069e-97 BLAST-P53757-FALSE_POSITIVE-1.82024e-56 HMM-P34161-FALSE_POSITIVE-1.3e-06 HMM-P04807-TRUE_POSITIVE-4.4e-217 HMM-A8W7W6-FALSE_POSITIVE-1.4e-07 HMM-A8W7W6-FALSE_POSITIVE-1.4e-07 2.4.1.216-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P07265-FALSE_POSITIVE-2.33436e-90 BLAST-P38893-FALSE_POSITIVE-2.65198e-53 HMM-Q04116-FALSE_POSITIVE-5e-06 HMM-Q04409-FALSE_POSITIVE-1e-128 HMM-P32466-FALSE_POSITIVE-1.4e-07 HMM-P32466-FALSE_POSITIVE-1.4e-07 HMM-P40884-FALSE_POSITIVE-2.6e-131 HMM-P04397-TRUE_POSITIVE-3.3e-23 HMM-P07269-FALSE_POSITIVE-0.0001 HMM-P17709-FALSE_POSITIVE-7.2e-128 HMM-Q04162-FALSE_POSITIVE-1.6e-07 HMM-Q04162-FALSE_POSITIVE-1.6e-07 HMM-Q08295-FALSE_POSITIVE-2.1e-114 HMM-P53757-FALSE_POSITIVE-5.3e-13 HMM-Q06858-FALSE_POSITIVE-0.0001 HMM-P34161-FALSE_POSITIVE-1.3e-06 HMM-A8W7W8-FALSE_POSITIVE-1.6e-07 HMM-A8W7W8-FALSE_POSITIVE-1.6e-07 HMM-Q76CZ0-FALSE_POSITIVE-2.6e-114 HMM-P38893-FALSE_POSITIVE-6.1e-13 HMM-Q06204-TRUE_POSITIVE-0.00017 HMM-Q04116-FALSE_POSITIVE-5e-06 HMM-P13181-FALSE_POSITIVE-1.9e-07 HMM-P13181-FALSE_POSITIVE-1.9e-07 HMM-P40439-FALSE_POSITIVE-5.2e-114 HMM-P07269-FALSE_POSITIVE-0.0001 HMM-P32467-FALSE_POSITIVE-2.2e-07 HMM-P32467-FALSE_POSITIVE-2.2e-07 HMM-P53051-FALSE_POSITIVE-9e-114 HMM-Q06858-FALSE_POSITIVE-0.0001 MARIBOES-3.1.3.1-RXN-reactionStatus=TRUE_POSITIVE HMM-A8W7W2-FALSE_POSITIVE-2.2e-07 HMM-A8W7W2-FALSE_POSITIVE-2.2e-07 HMM-P53341-FALSE_POSITIVE-5.9e-98 HMM-Q06204-TRUE_POSITIVE-0.00017 List of predictions: HMM-P40885-FALSE_POSITIVE-2.4e-07 HMM-P40885-FALSE_POSITIVE-2.4e-07 HMM-P38158-FALSE_POSITIVE-1.2e-96 BLAST-P11491-TRUE_POSITIVE-4.33135e-102 HMM-P10870-FALSE_POSITIVE-2.4e-07 HMM-P10870-FALSE_POSITIVE-2.4e-07 HMM-P07265-FALSE_POSITIVE-3.8e-96 BLAST-Q66RD0-FALSE_POSITIVE-1.28731e-49 HMM-P38695-FALSE_POSITIVE-2.5e-07 HMM-P38695-FALSE_POSITIVE-2.5e-07 HMM-P11491-TRUE_POSITIVE-8.1e-29 HMM-A8W7W9-FALSE_POSITIVE-2.5e-07 HMM-A8W7W9-FALSE_POSITIVE-2.5e-07 HMM-Q66RD0-FALSE_POSITIVE-1.8e-28 HMM-A8W7W5-FALSE_POSITIVE-2.7e-07 HMM-A8W7W5-FALSE_POSITIVE-2.7e-07 HMM-P39003-FALSE_POSITIVE-2.8e-07 HMM-P39003-FALSE_POSITIVE-2.8e-07 HMM-P39004-FALSE_POSITIVE-2.8e-07 HMM-P39004-FALSE_POSITIVE-2.8e-07 HMM-A8W7W7-FALSE_POSITIVE-2.8e-07 HMM-A8W7W7-FALSE_POSITIVE-2.8e-07 HMM-P43581-FALSE_POSITIVE-3e-07 HMM-P43581-FALSE_POSITIVE-3e-07 HMM-A8W7W4-FALSE_POSITIVE-3e-07 HMM-A8W7W4-FALSE_POSITIVE-3e-07 HMM-P54862-FALSE_POSITIVE-3.2e-07 HMM-P54862-FALSE_POSITIVE-3.2e-07 HMM-P23585-FALSE_POSITIVE-3.8e-07 HMM-P23585-FALSE_POSITIVE-3.8e-07 HMM-A8W7W3-FALSE_POSITIVE-3.8e-07 HMM-A8W7W3-FALSE_POSITIVE-3.8e-07 HMM-P38142-FALSE_POSITIVE-8.6e-07 HMM-P38142-FALSE_POSITIVE-8.6e-07 HMM-Q6B2Y5-FALSE_POSITIVE-8.9e-07 HMM-Q6B2Y5-FALSE_POSITIVE-8.9e-07 HMM-P40886-FALSE_POSITIVE-1.5e-06 HMM-P40886-FALSE_POSITIVE-1.5e-06 HMM-P39924-FALSE_POSITIVE-2.9e-06 HMM-P39924-FALSE_POSITIVE-2.9e-06 HMM-P39932-FALSE_POSITIVE-3.6e-06 HMM-P39932-FALSE_POSITIVE-3.6e-06 HMM-P53631-FALSE_POSITIVE-4e-06 HMM-P53631-FALSE_POSITIVE-4e-06 HMM-Q66RC7-FALSE_POSITIVE-5.1e-06 HMM-Q66RC7-FALSE_POSITIVE-5.1e-06 HMM-P54854-FALSE_POSITIVE-5.4e-06 HMM-P54854-FALSE_POSITIVE-5.4e-06 HMM-P47185-FALSE_POSITIVE-6.9e-06 HMM-P47185-FALSE_POSITIVE-6.9e-06 HMM-P40441-FALSE_POSITIVE-7.7e-05 HMM-P40441-FALSE_POSITIVE-7.7e-05 HMM-P42833-FALSE_POSITIVE-0.0001 HMM-P42833-FALSE_POSITIVE-0.0001 HMM-P47043-FALSE_POSITIVE-0.00024 HMM-P47043-FALSE_POSITIVE-0.00024

2.4.1.216-RXN-reactionStatus=FALSE_NEGATIVE

TRE6PHYDRO-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P40884-FALSE_POSITIVE-1.53429e-116 BLAST-P53051-FALSE_POSITIVE-1.758e-107 BLAST-Q76CZ0-FALSE_POSITIVE-3.0747e-107 BLAST-Q08295-FALSE_POSITIVE-3.54533e-105 BLAST-P40439-FALSE_POSITIVE-4.78749e-105 BLAST-P53341-FALSE_POSITIVE-1.32762e-97 β-D-glucose 1-phosphate BLAST-P38158-FALSE_POSITIVE-3.83069e-97 β-D-glucose α-D-glucose 6-phosphate sucrose BLAST-P07265-FALSE_POSITIVE-2.33436e-90 HMM-P40884-FALSE_POSITIVE-2.6e-131 HMM-Q08295-FALSE_POSITIVE-2.1e-114 HMM-Q76CZ0-FALSE_POSITIVE-2.6e-114 HMM-P40439-FALSE_POSITIVE-5.2e-114 HMM-P53051-FALSE_POSITIVE-9e-114 HMM-P53341-FALSE_POSITIVE-5.9e-98 HMM-P38158-FALSE_POSITIVE-1.2e-96 HMM-P07265-FALSE_POSITIVE-3.8e-96

GLUCOKIN-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P17709-TRUE_POSITIVE-2.61228e-102 BLAST-Q04409-TRUE_POSITIVE-9.86416e-95 BETA-PHOSPHOGLUCOMUTASE-RXN-reactionStatus=FALSE_NEGATIVE BLAST-P04807-FALSE_POSITIVE-1.00134e-71 List of predictions: BLAST-P04806-FALSE_POSITIVE-1.5905e-67 GLUCOSE-6-PHOSPHATE-1-EPIMERASE-RXN-reactionStatus=TRUE_NEGATIVE HMM-Q86ZR7-FALSE_POSITIVE-3.7e-05 HMM-P17709-TRUE_POSITIVE-1.4e-111 HMM-P04806-FALSE_POSITIVE-1.1e-106 HMM-Q04409-TRUE_POSITIVE-1.1e-100 HMM-P04807-FALSE_POSITIVE-6.3e-97

β-D-glucose-6-phosphate

Pathway ID: Trehalose-Degradation-Saccharomyces cerevisiae L-tyrosine

TYROSINE-AMINOTRANSFERASE-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P23542-FALSE_POSITIVE-1.45936e-55 HMM-P47039-FALSE_POSITIVE-3e-06 HMM-P52892-FALSE_POSITIVE-5.2e-06 HMM-Q66RF8-FALSE_POSITIVE-6.1e-06 HMM-P52893-FALSE_POSITIVE-0.00014

TYRAMINOTRANS-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P23542-FALSE_POSITIVE-2.31821e-76 BLAST-Q01802-FALSE_POSITIVE-1.23529e-60 HMM-P23542-FALSE_POSITIVE-4.5e-109 HMM-Q01802-FALSE_POSITIVE-8.9e-64

4-hydroxyphenylpyruvate

4-HYDROXYPHENYLPYRUVATE-DIOXYGENASE-RXN-reactionStatus=FALSE_NEGATIVE 1.2.3.13-RXN-reactionStatus=TRUE_NEGATIVE

homogentisate 4-hydroxyphenylacetate

HOMOGENTISATE-12-DIOXYGENASE-RXN-reactionStatus=FALSE_NEGATIVE

4-maleyl-acetoacetate

MALEYLACETOACETATE-ISOMERASE-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-Q12390-FALSE_POSITIVE-1.4e-06 HMM-P23202-FALSE_POSITIVE-0.00059 HMM-Q8NIE6-FALSE_POSITIVE-0.00059 HMM-Q8NII7-FALSE_POSITIVE-0.00059 HMM-Q8NJQ9-FALSE_POSITIVE-0.00059

4-fumaryl-acetoacetate

FUMARYLACETOACETASE-RXN-reactionStatus=FALSE_NEGATIVE FUMARYLACETOACETASE-RXN-reactionStatus=FALSE_NEGATIVE

fumarate acetoacetate

Pathway ID: TYROSINE-DEG-Saccharomyces cerevisiae chorismate

CHORISMATEMUT-RXN-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P32178-TRUE_POSITIVE-1.44133e-41 HMM-P32452-FALSE_POSITIVE-1.9e-06

prephenate

PREPHENATE-TRANSAMINE-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P23542-FALSE_POSITIVE-2.31821e-76 PREPHENATEDEHYDROG-RXN-reactionStatus=FALSE_NEGATIVE BLAST-Q01802-FALSE_POSITIVE-1.23529e-60 HMM-P23542-FALSE_POSITIVE-4.5e-109 HMM-Q01802-FALSE_POSITIVE-8.9e-64

4-hydroxyphenylpyruvate L-arogenate

TYRAMINOTRANS-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: BLAST-P23542-FALSE_POSITIVE-2.31821e-76 RXN-5682-reactionStatus=TRUE_NEGATIVE BLAST-Q01802-FALSE_POSITIVE-1.23529e-60 HMM-P23542-FALSE_POSITIVE-4.5e-109 CYCLOHEXADIENYL-DEHYDROGENASE-RXN-reactionStatus=FALSE_NEGATIVE HMM-Q01802-FALSE_POSITIVE-8.9e-64

L-tyrosine

Pathway ID: TYROSINE-SYN-Saccharomyces cerevisiae chorismate

CHORPYRLY-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-Q02981-FALSE_POSITIVE-5e-11 HMM-Q06567-FALSE_POSITIVE-3e-09 HMM-P27697-FALSE_POSITIVE-5.8e-07

all-trans-nonaprenyl diphosphate all-trans-decaprenyl diphosphate all-trans-heptaprenyl diphosphate 4-hydroxybenzoate all-trans-octaprenyl diphosphate all-trans-hexaprenyl diphosphate

2.5.1.39-RXN-reactionStatus=POSSIBLE_NEGATIVE RXN-9230-reactionStatus=POSSIBLE_NEGATIVE 2.5.1.39-RXN-reactionStatus=POSSIBLE_NEGATIVE RXN-9222-reactionStatus=TRUE_NEGATIVE RXN-9230-reactionStatus=POSSIBLE_NEGATIVE RXN-9222-reactionStatus=TRUE_NEGATIVE 4OHBENZOATE-OCTAPRENYLTRANSFER-RXN-reactionStatus=POSSIBLE_NEGATIVE RXN-9003-reactionStatus=TRUE_NEGATIVE 4OHBENZOATE-OCTAPRENYLTRANSFER-RXN-reactionStatus=POSSIBLE_NEGATIVE RXN-9003-reactionStatus=TRUE_NEGATIVE

nonaprenyl-4-hydroxybenzoate 3-decaprenyl-4-hydroxybenzoate 3-heptaprenyl-4-hydroxybenzoate 3-octaprenyl-4-hydroxybenzoate 3-hexaprenyl-4-hydroxybenzoate

RXN-9278-reactionStatus=TRUE_NEGATIVE RXN-9238-reactionStatus=TRUE_NEGATIVE RXN-9279-reactionStatus=TRUE_NEGATIVE RXN-9231-reactionStatus=TRUE_NEGATIVE RXN-9286-reactionStatus=TRUE_NEGATIVE RXN-9223-reactionStatus=TRUE_NEGATIVE RXN-9277-reactionStatus=TRUE_NEGATIVE 3-OCTAPRENYL-4-OHBENZOATE-DECARBOX-RXN-reactionStatus=TRUE_NEGATIVE RXN3O-58-reactionStatus=TRUE_NEGATIVE

3-nonaprenyl-4,5-dihydroxybenzoate 2-nonaprenylphenol 3-decaprenyl-4,5-dihydroxybenzoate 2-decaprenylphenol 3-heptaprenyl-4,5-dihydroxybenzoate 2-heptaprenylphenol 3-octaprenyl-4,5-dihydroxybenzoate 2-octaprenylphenol 3-hexaprenyl-4,5-dihydroxybenzoate

RXN-9281-reactionStatus=TRUE_POSITIVE RXN-9287-reactionStatus=TRUE_POSITIVE RXN-9280-reactionStatus=TRUE_POSITIVE 2.1.1.114-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: List of predictions: List of predictions: RXN-9239-reactionStatus=TRUE_NEGATIVE RXN-9282-reactionStatus=FALSE_NEGATIVE RXN-9232-reactionStatus=TRUE_NEGATIVE RXN-9224-reactionStatus=TRUE_NEGATIVE 2-OCTAPRENYLPHENOL-HYDROX-RXN-reactionStatus=FALSE_NEGATIVE HMM-P27680-TRUE_POSITIVE-1.4e-05 HMM-P27680-TRUE_POSITIVE-9.2e-06 HMM-P27680-TRUE_POSITIVE-8.9e-05 HMM-P27680-TRUE_POSITIVE-6.7e-06

3-nonaprenyl-4-hydroxy-5-methoxybenzoate 2-nonaprenyl-6-hydroxyphenol 3-decaprenyl-4-hydroxy-5-methoxybenzoate 2-decaprenyl-6-hydroxyphenol 3-heptaprenyl-4-hydroxy-5-methoxybenzoate 2-heptaprenyl-6-hydroxyphenol 3-octaprenyl-4-hydroxy-5-methoxybenzoate 2-octaprenyl-6-hydroxyphenol 3-hexaprenyl-4-hydroxy-5-methoxybenzoate

RXN-9284-reactionStatus=TRUE_NEGATIVE RXN-9240-reactionStatus=TRUE_NEGATIVE RXN-9285-reactionStatus=TRUE_NEGATIVE RXN-9233-reactionStatus=TRUE_NEGATIVE RXN-9288-reactionStatus=TRUE_NEGATIVE RXN-9225-reactionStatus=TRUE_NEGATIVE RXN-9283-reactionStatus=TRUE_NEGATIVE 2-OCTAPRENYL-6-OHPHENOL-METHY-RXN-reactionStatus=TRUE_NEGATIVE RXN3O-73-reactionStatus=TRUE_NEGATIVE

2-nonaprenyl-6-methoxyphenol 2-decaprenyl-6-methoxyphenol 2-heptaprenyl-6-methoxyphenol 2-octaprenyl-6-methoxyphenol 2-hexaprenyl-6-methoxyphenol

RXN-9241-reactionStatus=TRUE_NEGATIVE RXN-9234-reactionStatus=TRUE_NEGATIVE RXN-9226-reactionStatus=TRUE_NEGATIVE 2-OCTAPRENYL-6-METHOXYPHENOL-HYDROX-RXN-reactionStatus=TRUE_NEGATIVE RXN3O-12-reactionStatus=TRUE_NEGATIVE

2-nonaprenyl-6-methoxy-1,4-benzoquinol 2-decaprenyl-6-methoxy-1,4-benzoquinol 2-heptaprenyl-6-methoxy-1,4-benzoquinone 2-octaprenyl-6-methoxy-1,4-benzoquinol 2-hexaprenyl-6-methoxy-1,4-benzoquinol

RXN-9242-reactionStatus=TRUE_NEGATIVE RXN-9235-reactionStatus=TRUE_NEGATIVE RXN-9227-reactionStatus=TRUE_NEGATIVE 2-OCTAPRENYL-METHOXY-BENZOQ-METH-RXN-reactionStatus=TRUE_NEGATIVE RXN3O-54-reactionStatus=TRUE_NEGATIVE

2-nonaprenyl-3-methyl-6-methoxy-1,4-benzoquinol 2-decaprenyl-3-methyl-6-methoxy-1,4-benzoquinol 2-heptaprenyl-3-methyl-6-methoxy-1,4-benzoquinol 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinol 2-hexaprenyl-3-methyl-6-methoxy-1,4-benzoquinol

RXN-9243-reactionStatus=TRUE_NEGATIVE RXN-9236-reactionStatus=TRUE_NEGATIVE RXN-9228-reactionStatus=TRUE_NEGATIVE OCTAPRENYL-METHYL-METHOXY-BENZOQ-OH-RXN-reactionStatus=FALSE_NEGATIVE RXN3O-75-reactionStatus=TRUE_NEGATIVE

3-demethylubiquinol-9 3-demethylubiquinol-10 3-demethylubiquinol-7 3-demethylubiquinol-8 2-hexaprenyl-3-methyl-5-hydroxy-6-methoxy-1,4-benzoquinol

2.1.1.64-RXN-reactionStatus=FALSE_NEGATIVE RXN-9237-reactionStatus=FALSE_NEGATIVE RXN-9229-reactionStatus=FALSE_NEGATIVE DHHB-METHYLTRANSFER-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: List of predictions: List of predictions: List of predictions: RXN3O-102-reactionStatus=TRUE_NEGATIVE HMM-P27680-FALSE_POSITIVE-3.9e-42 HMM-P27680-FALSE_POSITIVE-3.9e-42 HMM-P27680-FALSE_POSITIVE-3.9e-42 HMM-P27680-FALSE_POSITIVE-1.1e-34

ubiquinol-9 ubiquinol-10 ubiquinol-7 ubiquinol-8 ubiquinol-6

RXN-9347-reactionStatus=TRUE_NEGATIVE RXN-9348-reactionStatus=TRUE_NEGATIVE RXN-9345-reactionStatus=TRUE_NEGATIVE RXN-9346-reactionStatus=TRUE_NEGATIVE RXN3O-117-reactionStatus=TRUE_NEGATIVE

ubiquinone-9 ubiquinone-10 ubiquinone-7 ubiquinone-8 ubiquinone-6

Pathway ID: Ubiquinone-Biosynthesis-Saccharomyces cerevisiae urea

UREA-CARBOXYLASE-RXN-reactionStatus=POSSIBLE_NEGATIVE

UREASE-RXN-reactionStatus=FALSE_NEGATIVE urea-1-carboxylate

ALLOPHANATE-HYDROLASE-RXN-reactionStatus=POSSIBLE_NEGATIVE

ammonia

Pathway ID: Urea-Degradation-Saccharomyces cerevisiae 2-keto-isovalerate

RXN-7643-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P06169-FALSE_POSITIVE-0 BLAST-P16467-FALSE_POSITIVE-0 BLAST-P26263-FALSE_POSITIVE-0 BRANCHED-CHAINAMINOTRANSFERVAL-RXN-reactionStatus=TRUE_POSITIVE BLAST-Q07471-FALSE_POSITIVE-0 List of predictions: BLAST-Q06408-FALSE_POSITIVE-1.4799e-90 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 BLAST-P32896-TRUE_POSITIVE-2.06555e-74 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 1.2.1.25-RXN-reactionStatus=TRUE_NEGATIVE BLAST-P87013-FALSE_POSITIVE-2.02268e-60 MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-P06169-FALSE_POSITIVE-0 List of predictions: MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P16467-FALSE_POSITIVE-0 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 List of predictions: BLAST-P32473-FALSE_POSITIVE-2.33193e-65 HMM-P26263-FALSE_POSITIVE-0 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-Q07471-FALSE_POSITIVE-4.4e-222 HMM-P47176-TRUE_POSITIVE-3.7e-162 MARIBOES-2.6.1.42-RXN-reactionStatus=TRUE_POSITIVE HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P16387-FALSE_POSITIVE-6.7e-11 HMM-Q06408-FALSE_POSITIVE-2.3e-95 HMM-P38891-TRUE_POSITIVE-7.5e-157 List of predictions: HMM-P16387-FALSE_POSITIVE-6.7e-11 HMM-Q12017-FALSE_POSITIVE-5e-13 BLAST-P47176-TRUE_POSITIVE-1.49811e-110 HMM-P07342-FALSE_POSITIVE-4.8e-09 BLAST-P38891-TRUE_POSITIVE-2.41111e-109 HMM-P39994-FALSE_POSITIVE-2.7e-08 HMM-P47176-TRUE_POSITIVE-3.7e-162 HMM-Q45U28-FALSE_POSITIVE-7.5e-06 HMM-P38891-TRUE_POSITIVE-7.5e-157 HMM-P53238-FALSE_POSITIVE-8.4e-06 HMM-Q04773-FALSE_POSITIVE-2.5e-05 HMM-P25040-FALSE_POSITIVE-0.00031 HMM-Q04004-FALSE_POSITIVE-0.00044

isobutanal isobutyryl-CoA L-valine

RXN-7657-reactionStatus=TRUE_POSITIVE List of predictions: BLAST-P38113-TRUE_POSITIVE-0 BLAST-P07246-TRUE_POSITIVE-1.19444e-169 BLAST-P00331-TRUE_POSITIVE-2.2163e-166 BLAST-P00330-TRUE_POSITIVE-3.09529e-165 BLAST-P10127-TRUE_POSITIVE-3.11897e-131 BLAST-P32771-TRUE_POSITIVE-1.62685e-123 BLAST-Q04018-FALSE_POSITIVE-2.98645e-81 HMM-P32771-TRUE_POSITIVE-1e-121 HMM-P00331-TRUE_POSITIVE-3.2e-112 HMM-P00330-TRUE_POSITIVE-6.9e-111 HMM-P07246-TRUE_POSITIVE-4.8e-110 HMM-P38113-TRUE_POSITIVE-1.7e-106 MARIBOES-1.1.1.1-RXN-reactionStatus=TRUE_POSITIVE HMM-Q07993-FALSE_POSITIVE-4.5e-26 List of predictions: HMM-Q04894-FALSE_POSITIVE-2.9e-23 BLAST-P38113-TRUE_POSITIVE-0 HMM-P35497-FALSE_POSITIVE-9.5e-21 BLAST-P07246-TRUE_POSITIVE-1.19444e-169 HMM-Q07786-FALSE_POSITIVE-9.8e-21 BLAST-P00331-TRUE_POSITIVE-2.2163e-166 HMM-P25377-FALSE_POSITIVE-4.1e-15 BLAST-P00330-TRUE_POSITIVE-3.09529e-165 HMM-P39713-FALSE_POSITIVE-1.4e-08 BLAST-P10127-TRUE_POSITIVE-3.11897e-131 HMM-Q6B208-FALSE_POSITIVE-3.7e-07 BLAST-P32771-TRUE_POSITIVE-1.62685e-123 HMM-P38230-FALSE_POSITIVE-4.3e-07 BLAST-Q04018-FALSE_POSITIVE-2.98645e-81 HMM-P39714-FALSE_POSITIVE-7.6e-07 HMM-P32771-TRUE_POSITIVE-1e-121 HMM-P00331-TRUE_POSITIVE-3.2e-112 HMM-P00330-TRUE_POSITIVE-6.9e-111 MARIBOES-1.1.1.1-RXN-reactionStatus=TRUE_POSITIVE HMM-P07246-TRUE_POSITIVE-4.8e-110 List of predictions: HMM-P38113-TRUE_POSITIVE-1.7e-106 BLAST-P38113-TRUE_POSITIVE-0 HMM-Q07993-FALSE_POSITIVE-4.5e-26 BLAST-P07246-TRUE_POSITIVE-1.19444e-169 HMM-Q04894-FALSE_POSITIVE-2.9e-23 BLAST-P00331-TRUE_POSITIVE-2.2163e-166 HMM-P35497-FALSE_POSITIVE-9.5e-21 BLAST-P00330-TRUE_POSITIVE-3.09529e-165 HMM-Q07786-FALSE_POSITIVE-9.8e-21 BLAST-P10127-TRUE_POSITIVE-3.11897e-131 HMM-P25377-FALSE_POSITIVE-4.1e-15 BLAST-P32771-TRUE_POSITIVE-1.62685e-123 HMM-P39713-FALSE_POSITIVE-6.6e-07 BLAST-Q04018-FALSE_POSITIVE-2.98645e-81 HMM-Q6B208-FALSE_POSITIVE-2.4e-05 HMM-P32771-TRUE_POSITIVE-1e-121 HMM-P38230-FALSE_POSITIVE-2.7e-05 MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE HMM-P00331-TRUE_POSITIVE-3.2e-112 HMM-P39714-FALSE_POSITIVE-4.3e-05 HMM-P00330-TRUE_POSITIVE-6.9e-111 MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE HMM-P07246-TRUE_POSITIVE-4.8e-110 List of predictions: List of predictions: HMM-P38113-TRUE_POSITIVE-1.7e-106 MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 HMM-Q07993-FALSE_POSITIVE-4.5e-26 List of predictions: BLAST-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 MEPROPCOA-FAD-RXN-reactionStatus=TRUE_NEGATIVE HMM-Q04894-FALSE_POSITIVE-2.9e-23 BLAST-P32771-FALSE_POSITIVE-3.01743e-85 BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P35497-FALSE_POSITIVE-9.5e-21 BLAST-P38715-FALSE_POSITIVE-5.93767e-64 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-Q07786-FALSE_POSITIVE-9.8e-21 BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-P25377-FALSE_POSITIVE-4.1e-15 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P39713-FALSE_POSITIVE-6.6e-07 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 HMM-P38137-FALSE_POSITIVE-3.9e-12 HMM-P38137-FALSE_POSITIVE-3.9e-12 HMM-Q6B208-FALSE_POSITIVE-2.4e-05 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 HMM-P38230-FALSE_POSITIVE-2.7e-05 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 HMM-P39714-FALSE_POSITIVE-4.3e-05 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-Q12458-FALSE_POSITIVE-2.3e-81 HMM-P38715-FALSE_POSITIVE-7.3e-68 MARIBOES-1.1.1.2-RXN-reactionStatus=TRUE_POSITIVE HMM-P38115-FALSE_POSITIVE-1.5e-53 List of predictions: HMM-Q04894-TRUE_POSITIVE-1.4e-49 BLAST-P32771-FALSE_POSITIVE-3.01743e-85 HMM-P25377-TRUE_POSITIVE-1e-43 BLAST-P38715-FALSE_POSITIVE-5.93767e-64 HMM-P47137-FALSE_POSITIVE-5.6e-23 BLAST-Q12458-FALSE_POSITIVE-2.97168e-62 HMM-Q07551-FALSE_POSITIVE-8.6e-13 BLAST-P14065-FALSE_POSITIVE-3.63052e-62 HMM-P00331-FALSE_POSITIVE-7.6e-12 BLAST-Q04894-TRUE_POSITIVE-1.11748e-49 HMM-P00330-FALSE_POSITIVE-1.4e-10 BLAST-P25377-TRUE_POSITIVE-3.72113e-44 HMM-P38113-FALSE_POSITIVE-2.3e-10 BLAST-P38115-FALSE_POSITIVE-1.6528e-43 HMM-P07246-FALSE_POSITIVE-4.2e-10 HMM-P14065-FALSE_POSITIVE-1.2e-84 HMM-Q07786-FALSE_POSITIVE-1.2e-08 HMM-Q12458-FALSE_POSITIVE-2.3e-81 HMM-P35497-FALSE_POSITIVE-1.3e-08 HMM-P38715-FALSE_POSITIVE-7.3e-68 HMM-Q07993-FALSE_POSITIVE-1.7e-08 HMM-P38115-FALSE_POSITIVE-1.5e-53 HMM-P32771-FALSE_POSITIVE-1.6e-07 HMM-Q04894-TRUE_POSITIVE-1.4e-49 HMM-P39713-FALSE_POSITIVE-4.9e-06 HMM-P25377-TRUE_POSITIVE-1e-43 HMM-P39714-FALSE_POSITIVE-2.4e-05 HMM-P47137-FALSE_POSITIVE-5.6e-23 HMM-Q6B208-FALSE_POSITIVE-2.7e-05 HMM-Q07551-FALSE_POSITIVE-8.6e-13 HMM-P00331-FALSE_POSITIVE-7.6e-12 HMM-P00330-FALSE_POSITIVE-1.4e-10 HMM-P38113-FALSE_POSITIVE-2.3e-10 HMM-P07246-FALSE_POSITIVE-4.2e-10 HMM-Q07786-FALSE_POSITIVE-1.2e-08 HMM-P35497-FALSE_POSITIVE-1.3e-08 HMM-Q07993-FALSE_POSITIVE-1.7e-08 HMM-P32771-FALSE_POSITIVE-1.6e-07 HMM-P39713-FALSE_POSITIVE-4.9e-06 HMM-P39714-FALSE_POSITIVE-2.4e-05 HMM-Q6B208-FALSE_POSITIVE-2.7e-05

MARIBOES-1.1.1.265-RXN-reactionStatus=TRUE_NEGATIVE

isobutanol isobutyrate methylacrylyl-CoA

METHYLACYLYLCOA-HYDROXY-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: HMM-P28817-FALSE_POSITIVE-5e-11 HMM-P53196-FALSE_POSITIVE-5.6e-10 HMM-Q08558-FALSE_POSITIVE-3.3e-06 HMM-Q05871-FALSE_POSITIVE-5.3e-06

3-hydroxy-isobutyryl-CoA

3-HYDROXYISOBUTYRYL-COA-HYDROLASE-RXN-reactionStatus=FALSE_NEGATIVE

3-hydroxy-isobutyrate

3-HYDROXYISOBUTYRATE-DEHYDROGENASE-RXN-reactionStatus=FALSE_NEGATIVE

methylmalonate-semialdehyde

1.2.1.27-RXN-reactionStatus=FALSE_NEGATIVE 1.2.1.27-RXN-reactionStatus=FALSE_NEGATIVE List of predictions: List of predictions: BLAST-P46367-FALSE_POSITIVE-1.1468e-70 BLAST-P46367-FALSE_POSITIVE-1.1468e-70 BLAST-P40047-FALSE_POSITIVE-1.53662e-68 BLAST-P40047-FALSE_POSITIVE-1.53662e-68 BLAST-P54115-FALSE_POSITIVE-9.25025e-64 BLAST-P54115-FALSE_POSITIVE-9.25025e-64 BLAST-A9LRZ7-FALSE_POSITIVE-9.25025e-64 BLAST-A9LRZ7-FALSE_POSITIVE-9.25025e-64 BLAST-P38067-FALSE_POSITIVE-5.8024e-61 BLAST-P38067-FALSE_POSITIVE-5.8024e-61 BLAST-P47771-FALSE_POSITIVE-1.50298e-58 BLAST-P47771-FALSE_POSITIVE-1.50298e-58 BLAST-P54114-FALSE_POSITIVE-1.7622e-56 BLAST-P54114-FALSE_POSITIVE-1.7622e-56 BLAST-P38694-FALSE_POSITIVE-5.06474e-42 BLAST-P38694-FALSE_POSITIVE-5.06474e-42 HMM-P40047-FALSE_POSITIVE-4.6e-54 HMM-P40047-FALSE_POSITIVE-4.6e-54 HMM-P46367-FALSE_POSITIVE-2.2e-48 HMM-P46367-FALSE_POSITIVE-2.2e-48 HMM-P47771-FALSE_POSITIVE-9.9e-42 HMM-P47771-FALSE_POSITIVE-9.9e-42 HMM-P54114-FALSE_POSITIVE-9e-38 HMM-P54114-FALSE_POSITIVE-9e-38 HMM-P38067-FALSE_POSITIVE-1.6e-37 HMM-P38067-FALSE_POSITIVE-1.6e-37 HMM-P54115-FALSE_POSITIVE-1.1e-34 HMM-P54115-FALSE_POSITIVE-1.1e-34 HMM-A9LRZ7-FALSE_POSITIVE-1.1e-34 HMM-A9LRZ7-FALSE_POSITIVE-1.1e-34 HMM-P38694-FALSE_POSITIVE-7e-23 HMM-P38694-FALSE_POSITIVE-7e-23 HMM-P32872-FALSE_POSITIVE-4.8e-12 HMM-P32872-FALSE_POSITIVE-4.8e-12 HMM-P07275-FALSE_POSITIVE-3.9e-10 HMM-P07275-FALSE_POSITIVE-3.9e-10 HMM-Q04458-FALSE_POSITIVE-6.9e-07 HMM-Q04458-FALSE_POSITIVE-6.9e-07

propionyl-CoA bicarbonate

MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE MARIBOES-3.1.2.20-RXN-reactionStatus=TRUE_NEGATIVE

MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE MARIBOES-6.2.1.1-RXN-reactionStatus=TRUE_POSITIVE List of predictions: List of predictions: MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE MARIBOES-1.2.4.4-RXN-reactionStatus=FALSE_NEGATIVE BLAST-Q66RJ0-FALSE_POSITIVE-0 BLAST-Q66RJ0-FALSE_POSITIVE-0 List of predictions: List of predictions: BLAST-P52910-TRUE_POSITIVE-0 BLAST-P52910-TRUE_POSITIVE-0 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-P32473-FALSE_POSITIVE-2.33193e-65 BLAST-Q01574-TRUE_POSITIVE-0 BLAST-Q01574-TRUE_POSITIVE-0 HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P32473-FALSE_POSITIVE-1.1e-55 HMM-P52910-TRUE_POSITIVE-0 HMM-P52910-TRUE_POSITIVE-0 HMM-P16387-FALSE_POSITIVE-6.7e-11 HMM-P16387-FALSE_POSITIVE-6.7e-11 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q01574-TRUE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-Q66RJ0-FALSE_POSITIVE-0 HMM-P38137-FALSE_POSITIVE-3.9e-12 HMM-P38137-FALSE_POSITIVE-3.9e-12

propionate 2-oxobutanoate

Pathway ID: VALINE-DEG-Saccharomyces cerevisiae