SI Appendix

Index Calculating chemical attributes using EC-BLAST ...... 2 Chemical attributes in isomerase reactions ...... 3 Bond changes …...... 3 Reaction centres …...... 5 Substrates and products …...... 6 Comparative analysis …...... 7 Racemases and epimerases (EC 5.1) …...... 7 Intramolecular oxidoreductases (EC 5.3) …...... 8 Intramolecular transferases (EC 5.4) …...... 9 Supporting references …...... 10 Fig. S1. Overview …...... 11 Fig. S2. Analysis of bond changes …...... 12 Fig. S3. Analysis of reaction centres …...... 13 Fig. S4. Analysis of substrates and products …...... 14 Fig. S5. Comparative analysis of chemical attributes …...... 15 Fig. S6. Analysis of subclasses EC 5.1, 5.3 and 5.4 …...... 16 Fig. S7. Example of similarities between three isomerase reactions …...... 17 Fig. S8. Domain composition of isomerase structures …...... 18 Fig. S9. Isomerase reactions in the universe of enzyme function …...... 19 Table S1. Overall statistics of chemical attributes …...... 20 Table S2. Analysis of bond changes clusters …...... 21 Table S3. Analysis of reaction centres clusters …...... 22 Table S4. Analysis of substrates and products clusters …...... 23 Table S5. List of isomerase reactions …...... 24 - 45

1 Calculating chemical attributes using EC-BLAST Our new method EC-BLAST performs robust comparisons and similarity searching of chemical reactions in a quantitative manner using the following chemical attributes: bond changes, reaction centres and structures of substrates and products (Reaction curation and similarity section in Materials and methods, main text). EC-BLAST uses reaction files (Rxnfiles) as the input for four different algorithms that perform atom-atom mapping using the maximum common substructure (MCS) method. Bond changes are obtained automatically using the Dugundji-Ugi (DU) model. The best solution is chosen on the basis of the number of bond changes and fragments generated and bond energies according to the principle of minimum chemical distance. In the DU model, substrates and products are represented using bond-electron matrices where diagonal elements correspond to the number of free valence electrons and off-diagonal entries give the bond orders between atoms. The reaction matrix is obtained when the substrates matrix is subtracted from the products matrix. A positive element on this matrix indicates bond formation, whereas a negative element corresponds to bond cleavage. Changes in the stereochemistry of atoms and bonds, also known as stereochanges, are coded in parallel. Cleaved and formed bonds are indicated as lines connecting atoms, for instance C–C means a single carbon- carbon bond that is cleaved or formed in the reaction. Bond order changes are represented as double arrows connecting bonds, for example C–C↔C=C means a single carbon-carbon bond turning into double carbon-carbon bond or vice versa. Stereochanges are represented as atoms that change their absolute configuration, for instance C(R/S) means a carbon atom that changes from R to S configuration.

In order to obtain reaction centres, EC-BLAST calculates circular fingerprints around each non- hydrogen atoms present in bond changes at different levels. Reaction centres at level 0 simply comprise the atoms involved in bond changes, level 1 extends radially by one covalent bond from level 0, level 2 extends by two covalent bonds from level 0 … Finally, the full structure of the substrates and products of the reaction is also considered. The type and number of chemical attributes for each reaction are encoded in reaction fingerprints and a Tanimoto score is used to compare reaction fingerprints and calculate similarities on the basis of bond changes, reaction centres or reactant structure individually. The results are stored in similarity matrices. An example illustrating the calculation of chemical attributes and similarities between three isomerase reactions is shown in Fig. S7.

2 Chemical attributes in isomerase reactions Summary statistics of the bond changes, reaction centres and substrates and products found in isomerase reactions are displayed in Table S1. Some chemical attributes (bond changes, reaction centres, or substrates and products) are distinctive of a particular EC subclass and we can quantify this as proportions of each chemical attribute across all the reactions present in a given isomerase subclass. Overall, twelve out of thirty bond changes (40%) found in isomerase reactions are distinctive for an isomerase EC subclass and this proportion increases from reaction centres (79%) to substrates and products (96%). The ability of the NC-IUBMB to manually update the EC classification in the form of new, transferred and deleted reactions as new enzyme data becomes available will change the proportion of chemical attributes for subclasses.

Bond changes Reactions and bond changes are distributed differently depending on the isomerase subclass (Fig. S2A). EC 5.4 (intramolecular transferases) is the most abundant subclass with 71 reactions, closely followed by EC 5.1 (racemases and epimerases) and EC 5.3 (intramolecular oxidoreductases) with 58 and 57 reactions, respectively. EC 5.4 has the largest number of bond changes followed by EC 5.3 and EC 5.5 (intramolecular lyases). The average number of bond changes per isomerase reaction is 7.3. There are several extreme cases with more than 20 bond changes, which correspond to complex reactions belonging to sub-subclass EC 5.4.99 (Fig. S2B). Isomerases from EC 5.1, 5.2 and 5.99 catalyse on average a small number of bond changes (1 to 8). However EC 5.3, 5.4 and 5.5 have more bond changes on average (Fig. S2C).

The optimal grouping of isomerase reactions was explored using hierarchical clustering (Reaction curation and similarity section in Materials and methods, main text). First, all-against-all pairwise similarities between isomerase reactions were computed using EC-BLAST on the basis of the number of bond changes (Fig. S2D). Reactions with the same type and number of bond changes are identical (similarity = 1), reactions with some bond changes in common have a similarity between 0 and 1, however reactions with no bond changes in common are different (similarity = 0). Similarities were stored in a matrix. Secondly, a clustering algorithm was applied to the similarity matrix in order to group similar reactions (Fig. S2E). After testing various clustering procedures by scanning how different cuts along the trees lead to greatest purity in EC subclasses, the Ward algorithm was selected to produce an optimal number of six chemically sensible clusters (Table S2). Only one cluster is pure in

3 subclasses: F in EC 5.1. Three clusters are more than 75% pure: A in EC 5.4, B in EC 5.2 and D in EC 5.3. Finally, two clusters are mixed: C (mainly EC 5.3 and 5.4) and E (EC 5.4 and 5.5). From the subclass point of view, almost all racemase and epimerase reactions (EC 5.1) group in cluster F. The only exception is EC 5.1.1.11, which takes part in cluster A and it is considered to be misannotated1 because of sharing identical bond changes to five intramolecular transferase reactions (EC 5.4) (see below). Cis-trans isomerase reactions (EC 5.2) are mostly grouped in cluster B. Exceptions are EC 5.2.1.5 (misannotated), 5.2.1.8 and 5.2.1.13 in cluster C. The rest of subclasses are mixed across several clusters, intramolecular oxidoreductases (EC 5.3) are present in four clusters: B, C, D and E; intramolecular transferases (EC 5.4) are in four clusters: A, C, D and E; intramolecular lyases (EC 5.5) are in three clusters: C, D and E; and other isomerases (EC 5.99) are in two clusters: C and D.

The bond change analysis questioned the EC subclass classification of 3 isomerase reactions:

• Located in cluster A, EC 5.1.1.11 corresponds to phenylalanine racemase, an enzyme catalysing the interconversion of L-phenylalanine and D-phenylalanine using ATP as a cofactor. As usual for a racemase (cluster F), this reaction has a C(R/S) stereochange as an attribute, however it also shares the presence of O–P and H–O with ten intramolecular transferase reactions (EC 5.4). Although the usage of ATP makes this enzyme unique among isomerases, its bond changes place it between two subclasses: racemases and epimerases (EC 5.1) and intramolecular transferases (EC 5.4).

• EC 5.3.3.7 is located in cluster B and corresponds to aconitate isomerase, which catalyses the transformation of trans-aconitate and cis-aconitate. It shares the presence of C(E/Z) with eight cis-trans isomerase reactions (EC 5.2). According to bond changes only, this biochemical transformation is closer to a cis-trans isomerase reaction than to an intramolecular oxidoreductase.

• Finally, EC 5.2.1.5 is in cluster C and corresponds to linoleate isomerase and catalyses the interconversion of linoleate and 9-cis,11-trans-octadecadienoate. As most cis-trans isomerases (EC 5.2) (cluster B), it has a bond change C(E/Z) as chemical attribute, however it also shares identical bond changes to three intramolecular oxidoreductase reactions (EC 5.3), namely EC 5.3.3.8, 5.3.3.13 and 5.3.3.14. 1 See Table S2.

4 Reaction centres The distribution and clustering of isomerase reactions by reaction centres looks similar to the distribution and clustering by bond changes. The six isomerase subclasses have different numbers of reactions centres (Fig. S3A). Intramolecular transferases (EC 5.4), followed by intramolecular oxidoreductases (EC 5.3) are the most populous subclasses by means of reaction centres. Then, medium-size subclasses are intramolecular lyases (EC 5.5) accounting for 666 reaction centres and racemases and epimerases (EC 5.1) with 420 reaction centres. Ultimately, cis-trans isomerases (EC 5.2) and other isomerases (EC 5.99) have a smaller number of reaction centres.

Reaction centres also show a clear distinction between EC 5.1 and 5.2, which are less diverse, and the rest of subclasses (Fig. S3B). The number of reaction centres per isomerase reaction ranges from 6 to 132. It is by definition always an even number due to the atom-atom mapping between the substrates and products of the reaction. The average number of reaction centres per isomerase reaction is 29 and there are a few extreme intramolecular transferases (EC 5.4) with 114, 120 and 132 reaction centres. In general, racemases and epimerases (EC 5.1) and cis-trans isomerases (EC 5.2) catalyse either 6 or 12 reaction centres, whereas the rest of subclasses range from 18 to 132 (Fig. S3C).

Reaction centres were named using IUPAC nomenclature (1). Subclasses EC 5.1, 5.2 and 5.99 are connected with up to six among the most common reaction centres. For example, EC 5.2 involves carbon atom, propyl, prop-2-en-1-yl, 2-methylprop-2-en-1-yl, prop-1-en-1-ylidene and 2-methylprop- 1-en-1-ylidene. However, the rest of subclasses have many of the most common reaction centres, which underlines their broad chemical diversity. For instance, all of the top 30 reaction centres are present in EC 5.4 (Fig. S1B). On the whole, the top 22 reaction centres (up to 2,2-dimethylpropyl) are present in at least three subclasses, highlighting how enzymes from different subclasses can perform catalysis on the same reaction centre.

As in bond changes, rare reaction centres, for instance (3,3-dimethyloxiran-2-yl)methyl, are only present in one subclass (Fig. S1B). On the other hand, abundant reaction centres, such as 2- hydroxypropyl are distributed across more than one subclass. In the former case, there are 25 enzymes classified as intramolecular transferases acting on squalene derivatives (EC 5.4.99), which are active on (3,3-dimethyloxiran-2-yl)methyl as a reaction centre, for example, lanosterol synthase (EC 5.4.99.7).

5 However in the latter scenario, there are 102 isomerases from four different subclasses: EC 5.1, 5.3, 5.4, 5.5 catalysing isomerase reactions where 2-hydroxypropyl is a reaction centre.

Unlike bond changes, the distribution of reaction similarities based on reaction centres is normal with a mean similarity of 0.22 (Fig. S3D). The complete-linkage algorithm was selected to produce an optimal number of 10 clusters (Figs. S3E and F), which are summarised in Table S3. Seven clusters are pure in subclasses (B', C', D', G', H', I' and J') and three of them are singletons (D', H' and J'). The three remaining clusters are mixed. All subclasses are spread across more than one cluster. Racemases and epimerases (EC 5.1) is the subclass adopting the best clustering where 98% of reactions are placed in pure clusters whereas the rest are in mixed clusters. However, intramolecular oxidoreductases (EC 5.3) have most reactions assigned to mixed clusters.

Almost all the reactions (216 out of 219) have at least one carbon atom involved in bond changes (Fig. S1B). The three exceptions are the intramolecular transfer reactions catalysed by bisphosphoglycerate mutase (EC 5.4.2.4) and 2,3-diphosphoglycerate-dependent and independent phosphoglycerate mutase (EC 5.4.2.11 and 5.4.2.12) (see cluster G' in Fig. S3F), which catalyse the cleavage of O–P and O–H bonds only. This analysis discovered 11 reactions with distinct profiles of reaction centres (Table S3). For instance, situated in cluster A' aconitate isomerase (EC 5.3.3.7) shares at least two common reaction centres (carbon atom and 2-methylprop-2-en-1-yl) with furylfuramide isomerase (EC 5.2.1.6), beta-carotene isomerase (EC 5.2.1.14) and other cis-trans isomerases (EC 5.2) (see cluster B' in Fig. S3F) while remains distinct due to the presence of prop-2-en-1-yl and absence of prop-1-en-1-ylidene.

Although the analysis by bond changes identified three reactions that appear to be more similar to other isomerase subclasses and were labeled as misannotated (EC 5.1.1.11, 5.2.1.5 and 5.3.3.7), these have distinct profiles of reaction centres. Similarly, the two reactions annotated as distinct by bond changes remain distinct (EC 5.4.99.38) and turned into a singleton (EC 5.5.1.3) when using reaction centres. The clustering by reaction centres provides a more detailed view of the overall chemistry of isomerases and sorts discrepancies from bond changes.

Substrates and products The distribution of substrates and products in isomerase reactions is simple. Most isomerase reactions are unimolecular therefore the number of substrates and products doubles the number of reactions (Fig.

6 S4A). Intramolecular transferases (EC 5.4), followed by racemases and epimerases (EC 5.1) and intramolecular oxidoreductases (EC 5.3) are the subclasses containing more substrates and products. With a much smaller number of reactions, intramolecular lyases (EC 5.5), cis-trans isomerases (EC 5.2) and other isomerases (EC 5.99) involve few substrates and products.

The distribution of reaction similarities based on the structures of substrates and products is normal with a mean similarity of 0.32 (Fig. S4B). The best fit to isomerase subclasses was obtained using the complete-linkage algorithm in the form of five optimal clusters (Fig. S4C and D) summarised in Table S4. All five clusters are mixed containing reactions from two or more subclasses. Racemases and epimerases (EC 5.1) and intramolecular transferases (EC 5.4) are present in all clusters. Intramolecular oxidoreductases (EC 5.3), cis-trans isomerases (EC 5.2) and intramolecular lyases (EC 5.5) exist in four, three and two clusters, respectively. Finally, other isomerases (EC 5.99) are only present in cluster B''. More than 90% of the substrates and products are just involved in one isomerase reaction, therefore analysing outliers (distinct and misannotated reactions) is not helpful here.

Comparative analysis Similarity and clustering by bond changes are more similar to results by reaction centres than by substrates and products. First, although the similarity distributions (Figs. S2D, S3D and S4B) are all significantly different according to the Kolmogorov-Smirnov test (p<0.001), there is higher correlation between bond changes and reaction centres (Pearson’s correlation coefficient (r) = 0.51, p<0.001) than between bond changes and substrates and products (r = 0.21, p<0.001) (Fig. S5A and B). Second, clusters of isomerase reactions by bond changes are more similar to clusters by reaction centres than to clusters by substrates and products (Figs. S5C, D, E and F). Topological distances between clustering trees also confirm this observation. For example, bond change clusters A (11 reactions), D (20 reactions), E (37 reactions) and F (56 reactions) directly correspond to reaction centre clusters G', E', F' and C', respectively. However there is not a clear correspondence between clusters by bond changes and substrates and products.

Racemases and epimerases (EC 5.1) Fifty-eight racemases and epimerases catalyse chiral inversions between stereoisomers, also known as changes in absolute stereochemistry (R or S) of asymmetric carbon atoms. This subclass is divided into 4 sub-subclasses depending on the type of substrate. Racemases from EC 5.1.1 act on amino acids and

7 derivatives, EC 5.1.2 on hydroxy acids and derivatives, EC 5.1.3 on carbohydrates and derivatives and EC 5.1.99 on “other compounds”. The analysis of bond changes is simple, only three bond changes are involved, all EC 5.1 reactions have only C(R/S) with the exception of phenylalanine racemase (EC 5.1.1.11), which also catalyses O–P and O–H. The similarity and clustering analyses based on the 61 unique reaction centres and the 115 substrates and products suggest two complementary ways to explore these sub-subclasses (Fig. S6A).

Both approaches set EC 5.1.1 and 5.1.3 apart in two different clusters. EC 5.1.1 is characterised by 2- azanylidenepropyl as the most common reaction centre in amino acids as reactants. In contrast, EC 5.1.3 is characterised by 2-hydroxypropyl in sugars and derivatives. Some reactions share characteristic attributes of two sub-subclasses. For instance, epimerases acting on glucosamine and derivatives (EC 5.1.3.8, 5.1.3.9, 5.1.3.14 and 5.1.3.23) catalyse transformations of 2-azanylidenepropyl in sugar molecules but not in amino acids. Alternatively, threonine racemase (EC 5.1.1.6) acts on the amino acid threonine even though 2-hydroxypropyl is also a reaction centre. In addition, amino acid racemase (EC 5.1.1.10) and hydantoin racemase (EC 5.1.99.5) form a separate cluster in Fig. S6A because they catalyse reactions containing a generic substructure or R-group close to the reaction centre.

Although EC 5.1.2 reactions group with EC 5.1.3 due to the presence of the 2-hydroxypropyl, they cluster with EC 5.1.1 reactions in substrates and products because hydroxy acids resemble amino acids more than carbohydrates at the overall structure level. Exceptionally, the reaction catalysed by 3- hydroxybutyryl coenzyme A (CoA) epimerase (EC 5.1.2.3) groups with EC 5.1.99 reactions because they share CoA as a substructure. Lastly, the reactions catalysed by phenylalanine racemase (EC 5.1.1.11) and some sugar epimerases (EC 5.1.3.10 and 5.1.3.26) share a diphosphate moiety as substructure.

To summarise, this analysis shows a clear separation between the overall chemistry of EC 5.1.1 and 5.1.3 reactions. EC 5.1.2 and 5.1.99 are diverse and group with EC 5.1.1 and 5.1.3 depending on the metric.

Intramolecular oxidoreductases (EC 5.3) The larger number of chemical attributes of the 57 intramolecular oxidoreductases (EC 5.3) indicates a more diverse chemistry in comparison with EC 5.1 reactions. This subclass is divided in 5 sub-

8 subclasses. EC 5.3.1 interconvert aldoses and ketoses, EC 5.3.2 transform keto and enol groups, EC 5.3.3 and 5.3.4 transpose C=C and S–S bonds, respectively, and EC 5.3.99 act on other substrates. This subclass is characterised by 16 bond changes, 233 reaction centres and 104 substrates and products. Sub-subclass EC 5.3.4 contains only one reaction catalysed by protein disulfide-isomerase (EC 5.3.4.1). The substrate of this enzyme is a protein, which does not have a structure file available, therefore it is not considered in this study.

Cluster analysis indicates a clear distinction between the overall chemistry of EC 5.3.1 and 5.3.3 reactions (Fig. S6B). Although EC 5.3.2 reactions cluster with EC 5.3.1 and 5.3.3 in the analysis of bond changes, they solely group with EC 5.3.1 according to reaction centres but with EC 5.3.3 in substrates and products. For example, the reactions catalysed by TDP-6-deoxy-hex-4-ulose isomerase (EC 5.3.2.3) and TDP-4-oxo-6-deoxy-alpha-D-glucose-3,4-oxoisomerase (EC 5.3.2.4) share similar bond changes and reaction centres with EC 5.3.1 reactions, however the overall structure of their reactants resemble EC 5.3.3 reactions more closely. Similarly, the reaction catalysed by trans-2,3- dihydro-3-hydroxyanthranilate isomerase (EC 5.3.3.17) shares H–O and C–O↔C=O with EC 5.3.2 reactions. Finally, EC 5.3.99 reactions group with 5.3.1 and 5.3.3 in bond changes but form separate clusters in reaction centres and substrates and products. For instance, thiazole tautomerase (EC 5.3.99.10) catalyses a C=C transposition, which is the most common bond change in EC 5.3.3 reactions. However, prostaglandin A isomerase (EC 5.3.3.9) also catalyses a C=C transposition, but its substrate is (13E)-(15S)-15-hydroxy-9-oxoprosta-10,13-dienoate, which is structurally similar to prostaglandin H2, a common substrate in EC 5.3.99.

Intramolecular transferases (EC 5.4) The 71 intramolecular transferase reactions (EC 5.4) are grouped into 5 sub-subclasses depending on the nature of the transferred chemical group. EC 5.4.1 involve acyl groups, EC 5.4.2 transfer phospho groups, EC 5.4.3 shift amino groups, EC 5.4.4 involve hydroxy groups and last but not least, EC 5.4.99 transfer other groups. Chemically speaking, different types of bond changes and reaction centres result in a complex and diverse overall chemistry, especially the cyclisation reactions catalysed by oxidosqualene cyclases (Fig. S6C).

EC 5.4.1 contains only one reaction catalysed by lysolecithin acylmutase (EC 5.4.1.1). EC 5.4.2 reactions involve O–P bonds and group together according to bond changes and reactions centres,

9 however in the analysis of substrates and products they split into two groups according to acyclic and cyclic reactants, especially sugar phosphates. Interestingly, the reaction catalysed by phosphoenolpyruvate mutase (EC 5.4.2.9) sits apart from the rest of EC 5.4.2 reactions because it involves the formation of C–P bonds. This extra chemical ability has been extensively explored since it allows the biosynthesis of phosphonates in nature (2). EC 5.4.3 reactions involve C–N bonds and cluster by bond changes and reaction centres in a similar way that EC 5.4.2 reactions do, however the analysis of their substrates and products segregates them into acyclic and aromatic reactants. EC 5.4.4 are diverse and spread across multiple clusters. Finally, in order to dissect the complexity of EC 5.4.99 reactions, the clustering results suggest that splitting EC 5.4.99 into additional sub-subclasses would be sensible according to an overall chemistry point of view. First, the 25 oxidosqualene cyclisations (EC 5.4.99.X, X = 7, 8, 17, 31-37, 39-41 and 46-57) act on (S)-2,3-epoxysqualene and derivatives and their bond changes, reaction centres and substrates and products are different from EC 5.4.99 and the rest of the isomerase reactions. Second, the chemistry of the 16 RNA pseudouridine synthases (EC 5.4.99.X, X = 12, 19-30 and 42-45) also sets apart from the rest of the EC 5.4.99 reactions. These enzymes post- transcriptionally isomerise specific uridine residues to pseudouridine in RNA. They all share the same overall chemistry but differ in the type of RNA (tRNA or rRNA) and the sequence sites where modifications take place (3). For example, tRNA pseudouridine38-40 synthase (EC 5.4.99.12) isomerises the uridine residues at positions 38, 39 and 40 of nearly all tRNAs and it is the only reaction with structural data available in this analysis (Fig. S6C). Pseudouridine synthases were also recently found to regulate mRNA (4). Third, there are 6 mutases catalysing carbon rearrangements (EC 5.4.99.X, X = 1, 2, 4, 13, 14 and 18), which also share similar overall chemistry. Overall, these three distinct groups of reactions within EC 5.4.99 could sensibly be considered as three new sub-subclasses.

Supporting references 1. IUPAC (2014) Compendium of Chemical Terminology. Gold Book. 2nd Ed. doi:10.1351/goldbook. 2. Yu X, et al. (2013) Diversity and abundance of phosphonate biosynthetic genes in nature. Proc Natl Acad Sci U S A 110(51):20759–64. 3. Hamma T, Ferré-D’Amaré AR (2006) Pseudouridine synthases. Chem Biol 13(11):1125–35. 4. Carlile TM, et al. (2014) Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells. Nature 515(7525):143–146.

10 Fig. S1

A B C

O

CH 3 HO

NH2 EC subclass

Manual curation of isomerase reactions

Comparative analysis

5.3.99.8 5.4.99.9 5.3.99.4 5.99.1.4 5.4.99.9 5.4.99.3 5.4.1.1 5.3.1.6 5.3.1.6 5.3.1.23 5.3.1.25 5.3.1.25 5.3.1.23 5.3.1.16 5.3.1.14 5.3.1.27 5.5.1.4 5.3.1.24 5.3.1.20 5.3.1.14 5.3.1.7 5.3.1.1 5.3.1.3 5.3.3.12 5.3.1.15 5.3.1.17 5.3.1.8 5.3.1.13 5.3.1.4 5.3.1.21 5.3.1.12 5.3.1.22 5.3.1.9 5.5.1.4 5.3.1.5 5.3.99.4 5.4.99.11 5.3.1.7 5.4.2.7 5.3.1.3 5.3.1.15 5.4.2.2 5.4.2.5 5.5.1.6 5.4.2.8 5.3.1.8 5.4.2.6 5.3.1.4 5.3.1.12 5.4.2.10 5.3.99.5 5.3.1.9 5.4.99.16 5.3.1.5 5.4.4.2 5.3.99.7 5.4.99.12 5.3.99.3 5.4.2.1 5.3.99.2 5.4.99.3 5.5.1.11 5.5.1.7 5.99.1.4 5.3.1.27 5.5.1.5 5.3.1.16 5.5.1.1 5.3.1.24 5.5.1.2 5.3.99.9 5.3.99.3 5.3.99.2 5.3.99.8 5.3.1.1 5.5.1.10 5.3.1.17 5.3.99.6 5.3.1.13 5.3.99.5 5.3.1.21 5.3.3.1 5.3.1.22 5.5.1.9 5.4.99.17 5.3.3.12 5.4.2.9 5.5.1.13 5.3.3.10 5.5.1.12 5.3.2.1 5.5.1.14 5.5.1.8 5.3.2.2 5.4.99.5 5.4.99.7 5.3.99.6 5.4.99.8 5.4.2.9 5.5.1.11 5.5.1.7 5.3.3.10 5.5.1.6 5.3.2.1 5.5.1.5 5.3.2.2 5.3.3.6 5.5.1.1 5.5.1.2 5.3.3.11 5.3.99.9 5.3.3.2 5.2.1.9 5.3.3.3 5.3.3.14 5.2.1.6 5.3.3.7 5.3.3.8 5.5.1.10 5.2.1.5 5.3.3.13 5.3.3.9 5.4.99.17 5.2.1.9 5.5.1.13 5.2.1.6 5.5.1.12 5.3.3.7 5.2.1.2 5.5.1.14 5.3.3.2 5.2.1.1 5.3.3.5 5.2.1.4 5.5.1.8 5.2.1.10 5.3.1.20 5.4.1.2 5.3.3.6 5.4.99.11 5.3.3.11 5.4.99.16 5.4.4.2 5.4.99.14 5.3.3.9 5.3.3.3 5.3.3.1 5.3.3.4 5.3.3.14 5.3.3.5 5.4.1.2 5.3.3.8 5.2.1.5 5.4.99.5 5.3.3.13 5.5.1.3 5.4.4.3 5.2.1.2 5.4.4.1 5.2.1.1 5.2.1.4 5.4.99.12 5.2.1.10 5.4.99.18 5.4.2.1 5.3.3.4 5.5.1.9 5.1.1.1 5.4.99.14 5.4.99.7 5.4.99.1 5.4.99.8 5.4.99.2 5.4.99.4 5.4.99.1 5.4.99.2 5.4.3.8 5.4.99.4 5.4.99.13 5.99.1.1 5.4.99.13 5.4.3.3 5.99.1.1 5.3.99.7 5.4.3.5 5.4.4.3 5.4.3.4 5.4.3.2 5.4.4.1 5.4.3.7 5.4.99.18 5.4.3.8 5.4.3.6 5.4.3.3 5.4.1.1 5.4.2.7 5.4.3.5 5.4.3.4 5.4.2.3 5.4.3.2 5.4.2.5 5.4.2.2 5.4.3.7 5.4.2.8 5.4.3.6 5.1.1.11 5.4.2.10 5.1.3.8 5.1.1.11 5.4.2.6 5.1.3.9 5.4.2.4 5.1.1.18 5.1.1.15 5.1.1.10 5.1.99.4 5.1.1.14 5.1.3.8 5.1.1.17 5.1.3.9 5.1.1.13 5.1.1.12 5.1.1.18 5.1.1.15 5.1.3.14 5.1.1.14 5.1.1.7 5.1.1.5 5.1.1.17 5.1.1.4 5.1.1.13 5.1.1.12 5.1.1.3 5.1.3.14 5.1.1.2 5.1.1.1 5.1.1.7 5.1.1.5 5.1.1.9 5.1.1.4 5.1.1.8 5.1.1.3 5.1.1.16 5.1.1.6 5.1.1.2 5.1.1.1 5.1.1.10 5.1.1.9 5.1.99.4 5.1.99.3 5.1.2.1 5.1.1.8 5.1.99.1 5.1.1.16 5.1.99.3 5.1.2.4 5.1.99.1 5.1.2.6 5.1.2.5 5.1.2.4 5.1.2.6 5.1.2.3 5.1.2.5 5.1.2.2 5.1.2.3 5.1.2.1 5.1.99.2 5.1.2.2 5.1.2.1 5.1.3.19 5.1.99.2 5.1.3.16 5.1.3.17 5.1.3.19 5.1.3.15 5.1.3.10 5.1.3.16 5.1.3.12 5.1.3.17 5.1.3.20 5.1.3.22 5.1.3.10 5.1.3.11 5.1.3.2 5.1.3.12 5.1.3.1 5.1.3.21 5.1.3.4 5.1.3.5 5.1.3.20 5.1.3.22 5.1.3.18 5.1.3.2 5.1.3.13 5.1.3.11 5.1.3.3 5.1.3.1 5.1.3.6 5.1.3.6 5.1.3.7 5.1.3.7 5.1.3.15 5.1.3.21 5.1.3.4 5.1.3.5 5.1.3.3 5.1.1.6 5.5.1.3 5.1.3.18 5.4.2.3 5.4.2.4 5.1.3.13 5.1.3.1 5.1.3.2 5.2.1.1 5.2.1.2 EC classification Cluster analysis

Fig. S1. (A) General overview of the approach. Isomerase reactions were curated, reaction similarities were computed using EC-BLAST and a comparative study compared the clusters obtained using cluster analysis with the EC classification of isomerases. Finally, suggestions to improve the EC were proposed. Distribution of isomerase reactions by reaction centres (B) and reactants (C) in EC subclass. Only the 30 most common reaction centres and reactants are shown.

11 Fig. S2 A B F

Subclass 5.1 O − O(ring) O − P O − P < > O=P O − C=C C=O C − O(ring) < − > C=O C − C(ring) < − > C C − C(ring) < − > C C(ring) C(E/Z) C − O C − N C − O < > C=O C − C(ring) < − > C=C C − < > C=C C − C − C(ring) C − O(ring) C − H C(R/S) C − S < > C=S C − C(ring) < − > C C(aromatic) C − S C − P C − N(aromatic) C#N < − > C=N C − N(ring) < − > C N(ring) N − O 1 H − N H − O 5.4.2.11 5.4.2.4 5.2 5.4.2.12 5.4.2.10 5.4.2.5 5.1.1.11 5.3 5.4.2.8 5.4.2.2 A 5.4.2.3 5.4.2.6 5.4.2.7 5.4 5.2.1.2 0.8 5.2.1.14 5.2.1.1 5.2.1.6 5.5 5.2.1.4 5.2.1.9 5.3.3.7 B 5.2.1.12 5.99 5.2.1.10 5.3.99.4 5.3.99.7 5.3.99.5 5.3.99.3 5.3.99.2 0.6 5.4.99.59 5.4.99.30 5.4.99.9 5.3.99.8 5.3.1.29 5.5.1.9 5.5.1.23 5.4.99.11 5.5.1.4 5.3.1.20 5.4.99.16 5.4.4.6 5.4.4.5 0.4 5.2.1.8 5.2.1.13 5.99.1.1 5.4.4.4 5.4.2.9 5.4.4.3 5.4.4.1 5.4.4.2 5.4.99.5 5.4.99.61 5.4.99.60 5.3.2.7 5.3.3.17 5.3.3.18 0.2 5.3.3.4 5.3.3.9 5.3.3.5 5.3.3.1 5.3.1.12 5.3.1.15 5.3.1.5 5.3.1.26 5.3.1.8 5.3.1.9 C 5.3.1.3 5.3.1.7 5.3.1.4 0 5.4.99.58 E 5.4.99.12 5.4.99.18 5.4.3.6 C 5.4.3.9 5.4.3.5 5.4.3.4 5.1.3.5 5.1.3.4 5.4.3.3 5.1.3.1 5.4.3.10 5.1.3.3 5.1.3.8 5.4.3.11 5.1.3.9 5.4.3.7 5.1.3.22 5.1.3.23 5.4.3.2 5.1.3.20 5.4.3.8 5.1.3.21 5.1.3.26 5.4.99.1 5.1.3.27 5.4.99.2 5.1.3.24 5.1.3.25 5.4.99.13 20 5.1.1.19 5.4.1.1 5.1.1.18 5.1.1.16 5.4.99.14 5.1.1.10 5.4.99.4 5.1.1.13 5.1.1.12 5.5.1.1 5.1.1.15 5.5.1.7 5.1.3.12 5.1.3.10 5.5.1.2 5.1.3.17 5.1.3.16 5.5.1.11 5.1.3.15 5.3.99.9 5.1.3.14 5.1.3.19 5.3.2.1 5.1.1.7 5.3.2.6 15 5.1.1.5 5.1.1.4 5.3.2.8 F 5.1.1.3 5.2.1.5 5.1.1.2 5.1.1.1 5.3.3.14 5.1.1.14 5.3.3.3 5.1.1.9 5.1.1.8 5.3.3.2 5.1.1.17 5.3.3.6 5.1.99.6 5.1.99.5 5.3.3.8 5.1.99.3 5.3.3.11 5.1.99.2 5.1.99.1 5.3.99.10 5.1.2.1 5.3.3.10 5.1.2.2 5.1.2.3 5.3.3.13 10 5.1.2.4 5.99.1.4 5.1.2.6 5.1.2.5 5.4.99.3 5.1.99.4 5.5.1.5 5.1.3.7 5.1.3.6 5.3.2.2 5.1.3.2 5.3.2.5 5.1.3.13 5.1.3.11 5.5.1.3 5.1.1.6 5.3.1.13 5.1.3.18 5.4.99.54 5.3.1.17 5.4.99.52 5.4.99.50 5.3.1.21 5.4.99.48 5.3.1.1 5.4.99.49 5.4.99.36 5.3.1.22 5 5.4.99.34 5.3.3.12 5.4.99.39 5.4.99.35 5.3.1.27 D 5.4.99.55 5.3.1.16 5.4.99.51 5.4.99.46 5.3.1.23 5.4.99.40 5.3.1.24 5.4.99.47 5.4.99.33 5.3.1.25 5.4.99.57 5.3.1.14 5.5.1.20 5.5.1.10 5.3.1.6 5.5.1.13 5.3.1.28 5.5.1.14 5.5.1.12 5.3.2.3 5.4.99.38 5.3.2.4 5.5.1.18 0 E 5.5.1.19 5.4.99.53 5.4.99.8 5.3.99.6 5.4.99.41 5.4.99.31 5.5.1.22 5.4.99.7 5.4.99.56 5.5.1.8 5.4.99.32 5.5.1.15 5.4.99.37 5.4.99.17 5.5.1.16 5.5.1.16 5.4.99.17 5.5.1.15 5.5.1.8 5.4.99.37 5.5.1.22 5.4.99.32 5.3.99.6 5.4.99.53 5.4.99.56 5.3.2.4 5.4.99.7 5.3.2.3 5.3.1.28 5.4.99.31 5.3.1.6 5.4.99.41 5.3.1.14 5.3.1.25 5.4.99.8 5.3.1.24 5.5.1.19 5.3.1.23 5.3.1.16 5.5.1.18 5.3.1.27 5.4.99.38 5.3.3.12 5.3.1.22 5.5.1.12 5.3.1.1 5.5.1.14 5.3.1.21 5.3.1.17 5.5.1.13 5.3.1.13 5.5.1.10 E D 5.5.1.3 5.3.2.5 5.5.1.20 5.3.2.2 5.5.1.5 5.4.99.57 5.4.99.3 5.4.99.33 D 5.99.1.4 5.4.99.47 5.3.3.13 5.3.3.10 5.4.99.40 5.3.99.10 5.3.3.11 5.4.99.46 5.3.3.8 5.4.99.51 5.3.3.6 5.3.3.2 5.4.99.55 5.3.3.3 5.4.99.35 5.3.3.14 5.2.1.5 5.4.99.39 5.3.2.8 5.4.99.34 5.3.2.6 5.3.2.1 5.4.99.36 5.3.99.9 5.4.99.49 5.5.1.11 5.5.1.2 5.4.99.48 5.5.1.7 5.4.99.50 5.5.1.1 5.4.99.4 5.4.99.52 5.4.99.14 5.4.99.54 5.4.1.1 5.4.99.13 5.1.3.18 5.4.99.2 5.4.99.1 5.1.1.6 5.4.3.8 5.1.3.11 5.4.3.2 5.4.3.7 5.1.3.13 5.4.3.11 5.1.3.2 5.4.3.10 5.4.3.3 5.1.3.6 5.4.3.4 5.1.3.7 5.4.3.5 5.4.3.9 5.1.99.4 5.4.3.6 5.1.2.5 5.4.99.18 5.4.99.12 5.1.2.6 5.4.99.58 5.1.2.4 5.3.1.4 5.3.1.7 5.1.2.3 5.3.1.3 5.1.2.2 5.3.1.9 5.3.1.8 5.1.2.1 5.3.1.26 5.1.99.1 5.3.1.5 5.3.1.15 5.1.99.2 5.3.1.12 5.1.99.3 5.3.3.1 C 5.3.3.5 5.1.99.5 5.3.3.9 5.1.99.6 5.3.3.4 5.3.3.18 5.1.1.17 5.3.3.17 5.3.2.7 5.1.1.8 5.4.99.60 5.1.1.9 5.4.99.61 5.4.99.5 5.1.1.14 5.4.4.2 5.1.1.1 5.4.4.1 5.4.4.3 5.1.1.2 5.4.2.9 5.1.1.3 5.4.4.4 5.99.1.1 5.1.1.4 5.2.1.13 5.1.1.5 5.2.1.8 5.4.4.5 5.1.1.7 5.4.4.6 5.1.3.19 5.4.99.16 5.3.1.20 5.1.3.14 F 5.5.1.4 5.1.3.15 5.4.99.11 5.5.1.23 5.1.3.16 5.5.1.9 5.1.3.17 5.3.1.29 5.3.99.8 5.1.3.10 5.4.99.9 5.1.3.12 5.4.99.30 5.4.99.59 5.1.1.15 5.3.99.2 5.3.99.3 5.1.1.12 5.3.99.5 5.1.1.13 5.3.99.7 5.3.99.4 5.1.1.10 5.2.1.10 5.1.1.16 5.2.1.12 5.3.3.7 5.1.1.18 5.2.1.9 5.1.1.19 5.2.1.4 5.2.1.6 5.1.3.25 5.2.1.1 5.1.3.24 5.2.1.14 B 5.2.1.2 5.1.3.27 5.4.2.7 5.1.3.26 5.4.2.6 5.4.2.3 5.1.3.21 5.4.2.2 5.1.3.20 5.4.2.8 5.1.1.11 5.1.3.23 5.4.2.5 5.1.3.22 5.4.2.10 5.4.2.12 5.1.3.9 5.4.2.4 5.1.3.8 5.4.2.11 5.1.3.5 5.1.3.4 5.1.3.1 5.1.3.3 5.1.3.8 5.1.3.9 5.1.3.22 5.1.3.23 5.1.3.20 5.1.3.21 5.1.3.26 5.1.3.27 5.1.3.24 5.1.3.25 5.1.1.19 5.1.1.18 5.1.1.16 5.1.1.10 5.1.1.13 5.1.1.12 5.1.1.15 5.1.3.12 5.1.3.10 5.1.3.17 5.1.3.16 5.1.3.15 5.1.3.14 5.1.3.19 5.1.1.7 5.1.1.5 5.1.1.4 5.1.1.3 5.1.1.2 5.1.1.1 5.1.1.14 5.1.1.9 5.1.1.8 5.1.1.17 5.1.99.6 5.1.99.5 5.1.99.3 5.1.99.2 5.1.99.1 5.1.2.1 5.1.2.2 5.1.2.3 5.1.2.4 5.1.2.6 5.1.2.5 5.1.99.4 5.1.3.7 5.1.3.6 5.1.3.2 5.1.3.13 5.1.3.11 5.1.1.6 5.1.3.18 5.4.99.54 5.4.99.52 5.4.99.50 5.4.99.48 5.4.99.49 5.4.99.36 5.4.99.34 5.4.99.39 5.4.99.35 5.4.99.55 5.4.99.51 5.4.99.46 5.4.99.40 5.4.99.47 5.4.99.33 5.4.99.57 5.5.1.20 5.5.1.10 5.5.1.13 5.5.1.14 5.5.1.12 5.4.99.38 5.5.1.18 5.5.1.19 5.4.99.8 5.4.99.41 5.4.99.31 5.4.99.7 5.4.99.56 5.4.99.32 5.4.99.37 5.4.99.17 5.5.1.16 5.5.1.15 5.5.1.8 5.5.1.22 5.3.99.6 5.4.99.53 5.3.2.4 5.3.2.3 5.3.1.28 5.3.1.6 5.3.1.14 5.3.1.25 5.3.1.24 5.3.1.23 5.3.1.16 5.3.1.27 5.3.3.12 5.3.1.22 5.3.1.1 5.3.1.21 5.3.1.17 5.3.1.13 5.5.1.3 5.3.2.5 5.3.2.2 5.5.1.5 5.4.99.3 5.99.1.4 5.3.3.13 5.3.3.10 5.3.99.10 5.3.3.11 5.3.3.8 5.3.3.6 5.3.3.2 5.3.3.3 5.3.3.14 5.2.1.5 5.3.2.8 5.3.2.6 5.3.2.1 5.3.99.9 5.5.1.11 5.5.1.2 5.5.1.7 5.5.1.1 5.4.99.4 5.4.99.14 5.4.1.1 5.4.99.13 5.4.99.2 5.4.99.1 5.4.3.8 5.4.3.2 5.4.3.7 5.4.3.11 5.4.3.10 5.4.3.3 5.4.3.4 5.4.3.5 5.4.3.9 5.4.3.6 5.4.99.18 5.4.99.12 5.4.99.58 5.3.1.4 5.3.1.7 5.3.1.3 5.3.1.9 5.3.1.8 5.3.1.26 5.3.1.5 5.3.1.15 5.3.1.12 5.3.3.1 5.3.3.5 5.3.3.9 5.3.3.4 5.3.3.18 5.3.3.17 5.3.2.7 5.4.99.60 5.4.99.61 5.4.99.5 5.4.4.2 5.4.4.1 5.4.4.3 5.4.2.9 5.4.4.4 5.99.1.1 5.2.1.13 5.2.1.8 5.4.4.5 5.4.4.6 5.4.99.16 5.3.1.20 5.5.1.4 5.4.99.11 5.5.1.23 5.5.1.9 5.3.1.29 5.3.99.8 5.4.99.9 5.4.99.30 5.4.99.59 5.3.99.2 5.3.99.3 5.3.99.5 5.3.99.7 5.3.99.4 5.2.1.10 5.2.1.12 5.3.3.7 5.2.1.9 5.2.1.4 5.2.1.6 5.2.1.1 5.2.1.14 5.2.1.2 5.4.2.7 5.4.2.6 A5.4.2.3 5.4.2.2 5.4.2.8 5.1.1.11 5.4.2.5 5.4.2.10 5.4.2.12 5.4.2.4 5.4.2.11 5.1.3.3 5.1.3.1 5.1.3.4 5.1.3.5

Fig. S2. Analysis of isomerase reactions on the basis of bond changes. (A) Total number of isomerase reactions (1st column) and bond changes (2nd column) across EC subclasses. Bars are coloured according to subclass. (B) Distribution of the number of isomerase reactions versus the number of bond changes. (C) Distribution of the number of bond changes per isomerase reaction in each EC subclass. The number of reactions belonging to each subclass is shown in brackets. Coloured boxes represent interquartile ranges. Error bars represent 1.5 times the interquartile range. Points beyond the error bars refer to outliers. Cluster analysis of isomerase reactions based on similarities by bond changes: (D) Distribution of pairwise similarities. (E) Bond change similarity matrix. Blue-to-red scale represents increasing similarity, identical reactions have a similarity of 1 (red). Reactions are annotated in colours according to their EC subclass (top row). Six clusters were identified (A to F). (F) Hierarchical clustering of isomerase reactions (rows) by bond changes (columns). The blue scale represents the number of bond changes in reactions. Reactions are annotated in colours according to their EC subclass (left-hand column). Bond changes were ordered left-to-right by increasing number. Outliers are annotated with an arrow (Table S2).

12 Fig. S3

A B F Subclass 1 5.1 5.2 − 3 (propan 2 yl)pentyl 2,3 − dimethyl − 2 yl)methyl (3,3 − dimethyloxiran − 2 en 1 yl 3 − methylbut − 2 yl)ethyl 2 − (3,3 dimethyloxiran − 2 yl)methyl (2,3 − dimethyloxiran 3 − tert− 2,2 dimethylpentyl − butyl − 2 ylmethyl oxiran − 2 yl)methyl (2 − methyloxiran 2,2 − dimethylpropyl [C]1[C]O1 methoxymethyl [C]C([O])[O] 2 − azanylidenepropyl − 3 en 1 yl 3 − methylpent 2 − oxopropyl − 3 en 1 yl 4 − methylpent dimethylpropyl 2 − hydroxyethyl oxomethylidene − 1 en ylidene 2 − methylprop prop − 1 en ylidene ethyl − 2 en 1 yl 2 − methylprop 2 − methylpropyl prop − 2 en 1 yl hydroxymethyl propyl 2 − hydroxypropyl atom oxygen carbon atom 5.3 0.8 5.4.99.14 5.3.3.3 5.4.99.1 5.4.99.2 5.4.99.13 5.4 5.4.99.4 5.3.3.6 5.3.3.11 5.3.3.2 5.5 5.5.1.19 5.3.3.5 5.3.3.1 5.2.1.5 5.3.3.14 5.99 0.6 5.3.3.8 5.3.3.4 5.3.3.9 5.2.1.6 5.3.3.7 5.2.1.14 5.2.1.12 A' 5.3.99.10 5.4.99.12 5.5.1.4 5.4.99.9 5.4.1.1 5.4.3.3 0.4 5.4.3.5 5.4.3.4 5.4.99.58 5.4.3.2 5.4.3.9 5.4.3.7 5.4.3.10 5.4.3.11 5.4.3.6 5.4.3.8 5.99.1.1 5.2.1.10 5.2.1.9 5.2.1.4 0.2 5.2.1.2 5.2.1.1 B' 5.1.2.5 5.1.2.6 5.1.2.4 5.1.3.17 5.1.3.19 5.1.2.3 5.1.2.1 5.1.99.2 5.1.3.12 5.1.3.10 5.1.3.1 5.1.3.22 0 5.1.3.27 5.1.3.4 E 5.1.3.20 5.1.3.5 5.1.3.26 C 5.1.3.16 5.1.3.25 5.1.3.6 5.1.3.2 5.1.3.7 5.1.3.13 5.2.1.8 5.1.3.18 5.4.99.18 5.4.4.1 5.1.99.4 H'I' J' 5.4.4.3 5.1.1.6 5.5.1.3 40 5.4.2.4 5.1.2.2 5.4.2.11 5.1.99.1 5.4.2.12 5.1.99.3 C' 5.4.2.8 5.4.2.3 5.1.1.10 5.4.2.10 5.4.2.7 5.1.99.5 5.4.2.6 5.1.99.6 5.4.2.5 5.1.1.4 G' 5.4.2.2 5.3.2.5 5.1.1.8 5.1.1.11 5.1.1.9 5.4.99.41 5.4.99.39 5.1.1.17 5.4.99.40 5.1.1.3 5.4.99.34 5.4.99.35 5.1.1.5 5.4.99.55 5.1.1.7 5.4.99.46 5.4.99.57 5.1.1.12 5.4.99.51 5.1.1.14 5.4.99.50 5.4.99.49 5.1.1.2 5.4.99.36 5.1.1.13 30 5.4.99.48 5.4.99.54 5.1.1.1 5.4.99.52 5.1.3.8 5.3.99.8 5.1.3.9 5.2.1.13 5.4.99.37 5.1.3.14 5.4.99.17 5.1.1.15 5.4.99.56 5.4.99.47 5.1.1.16 5.4.99.33 5.1.1.19 5.4.99.8 5.4.99.7 5.1.1.18 5.4.99.53 5.1.3.23 5.4.99.31 5.4.99.32 5.1.3.21 F' 5.5.1.9 5.1.3.15 5.5.1.10 5.4.99.38 5.1.3.3 5.5.1.18 5.1.3.11 5.4.99.60 5.4.99.61 5.1.3.24 5.5.1.8 5.3.1.8 5.5.1.22 5.3.1.26 5.5.1.13 20 5.5.1.14 5.3.1.9 D' 5.5.1.12 5.3.1.7 5.5.1.15 5.5.1.16 5.3.1.12 5.4.99.5 5.3.1.3 5.4.4.2 5.3.3.13 5.3.1.5 5.3.3.18 5.3.1.4 5.3.99.6 5.5.1.20 5.3.1.15 5.3.3.12 5.4.4.4 5.99.1.4 5.4.4.5 5.5.1.11 5.4.4.6 5.5.1.7 5.3.99.5 5.3.99.4 5.5.1.1 5.3.99.2 5.5.1.2 5.3.99.3 5.3.99.9 5.3.2.2 5.5.1.5 5.3.99.7 5.3.1.20 5.5.1.23 5.4.99.11 5.4.99.16 5.3.2.1 5.4.99.30 5.3.2.8 10 5.4.99.59 5.4.99.3 5.3.2.6 5.3.2.7 5.4.2.9 5.3.3.10 5.3.3.17 5.3.2.3 5.3.1.1 5.3.2.4 5.3.1.17 5.3.1.13 5.3.1.27 5.3.1.21 5.3.1.6 5.3.1.22 5.3.1.23 5.3.1.29 5.3.1.28 5.3.1.24 5.3.1.14 5.3.1.16 5.3.1.25 5.3.1.16 5.3.1.25 5.3.1.24 5.3.1.14 5.3.1.23 E' 5.3.1.6 5.3.1.28 E' 5.3.1.27 5.3.1.29 5.3.2.4 5.3.2.3 5.3.1.22 5.4.2.9 5.3.1.21 5.3.2.6 5.3.1.13 5.3.2.8 0 5.3.2.1 5.3.1.17 5.5.1.23 5.3.99.7 5.3.1.1 5.3.99.9 5.3.3.17 5.5.1.2 5.3.3.10 5.5.1.1 5.5.1.7 5.3.2.7 5.5.1.11 5.4.99.3 5.4.4.4 5.3.1.15 5.4.99.59 D 5.3.1.4 5.4.99.30 5.3.1.5 5.3.1.3 5.4.99.16 5.3.1.12 5.4.99.11 5.3.1.7 5.3.1.9 5.3.1.20 D' 5.3.1.26 5.5.1.5 5.3.1.8 5.1.3.24 5.3.2.2 5.1.3.11 5.3.99.3 5.1.3.3 5.1.3.15 5.3.99.2 5.1.3.21 5.3.99.4 5.1.3.23 5.3.99.5 5.1.1.18 5.1.1.19 5.4.4.6 5.1.1.16 5.4.4.5 5.1.1.15 5.1.3.14 5.99.1.4 5.1.3.9 5.3.3.12 5.1.3.8 5.1.1.1 5.5.1.20 5.1.1.13 5.3.99.6 5.1.1.2 5.1.1.14 5.3.3.18 5.1.1.12 5.3.3.13 5.1.1.7 5.1.1.5 5.4.4.2 5.1.1.3 5.4.99.5 5.1.1.17 5.1.1.9 5.5.1.16 5.1.1.8 5.5.1.15 5.1.1.4 5.5.1.12 5.1.99.6 5.1.99.5 5.5.1.14 5.1.1.10 5.5.1.13 5.1.99.3 5.1.99.1 5.5.1.22 5.1.2.2 5.5.1.8 5.1.1.6 5.1.99.4 5.4.99.61 C' 5.1.3.18 5.4.99.60 5.1.3.13 5.1.3.7 5.5.1.18 5.1.3.2 5.4.99.38 5.1.3.6 5.1.3.25 5.5.1.10 5.1.3.16 5.5.1.9 5.1.3.26 5.1.3.5 5.4.99.32 5.1.3.20 5.4.99.31 5.1.3.4 5.4.99.53 5.1.3.27 5.1.3.22 5.4.99.7 5.1.3.1 5.4.99.8 5.1.3.10 5.1.3.12 5.4.99.33 F' 5.1.99.2 5.4.99.47 5.1.2.1 5.1.2.3 5.4.99.56 5.1.3.19 5.4.99.17 5.1.3.17 5.1.2.4 5.4.99.37 5.1.2.6 5.2.1.13 5.1.2.5 5.2.1.1 5.3.99.8 5.2.1.2 5.4.99.52 5.2.1.4 5.4.99.54 B' 5.2.1.9 5.2.1.10 5.4.99.48 5.99.1.1 5.4.99.36 5.4.3.8 5.4.3.6 5.4.99.49 5.4.3.11 5.4.99.50 5.4.3.10 5.4.3.7 5.4.99.51 5.4.3.9 5.4.99.57 5.4.3.2 5.4.99.58 5.4.99.46 5.4.3.4 5.4.99.55 5.4.3.5 5.4.3.3 5.4.99.35 5.4.1.1 5.4.99.34 5.4.99.9 5.5.1.4 5.4.99.40 5.4.99.12 5.4.99.39 5.3.99.10 5.4.99.41 5.2.1.12 5.2.1.14 5.1.1.11 5.3.3.7 5.3.2.5 5.2.1.6 5.3.3.9 5.4.2.2 5.3.3.4 5.4.2.5 5.3.3.8 A' 5.3.3.14 5.4.2.6 5.2.1.5 5.4.2.7 5.3.3.1 5.3.3.5 5.4.2.10 5.5.1.19 5.4.2.3 5.3.3.2 G' 5.3.3.11 5.4.2.8 5.3.3.6 5.4.2.12 5.4.99.4 5.4.99.13 5.4.2.11 5.4.99.2 5.4.2.4 5.4.99.1 5.5.1.3 5.3.3.3 5.4.99.14 5.4.4.3 5.2.1.8 5.4.99.18 5.4.4.1 5.4.4.3 5.5.1.3 5.4.2.4 5.4.2.11 5.4.2.12 5.4.2.8 5.4.2.3 5.4.2.10 5.4.2.7 5.4.2.6 5.4.2.5 5.4.2.2 5.3.2.5 5.1.1.11 5.4.99.41 5.4.99.39 5.4.99.40 5.4.99.34 5.4.99.35 5.4.99.55 5.4.99.46 5.4.99.57 5.4.99.51 5.4.99.50 5.4.99.49 5.4.99.36 5.4.99.48 5.4.99.54 5.4.99.52 5.3.99.8 5.2.1.13 5.4.99.37 5.4.99.17 5.4.99.56 5.4.99.47 5.4.99.33 5.4.99.8 5.4.99.7 5.4.99.53 5.4.99.31 5.4.99.32 5.5.1.9 5.5.1.10 5.4.99.38 5.5.1.18 5.4.99.60 5.4.99.61 5.5.1.8 5.5.1.22 5.5.1.13 5.5.1.14 5.5.1.12 5.5.1.15 5.5.1.16 5.4.99.5 5.4.4.2 5.3.3.13 5.3.3.18 5.3.99.6 5.5.1.20 5.3.3.12 5.99.1.4 5.4.4.5 5.4.4.6 5.3.99.5 5.3.99.4 5.3.99.2 5.3.99.3 5.3.2.2 5.5.1.5 5.3.1.20 5.4.99.11 5.4.99.16 5.4.99.30 5.4.99.59 5.4.99.3 5.3.2.7 5.3.3.10 5.3.3.17 5.3.1.1 5.3.1.17 5.3.1.13 5.3.1.21 5.3.1.22 5.3.1.29 5.3.1.28 5.3.1.14 5.3.1.25 5.3.1.16 5.3.1.24 5.3.1.23 5.3.1.6 5.3.1.27 5.3.2.4 5.3.2.3 5.4.2.9 5.3.2.6 5.3.2.8 5.3.2.1 5.5.1.23 5.3.99.7 5.3.99.9 5.5.1.2 5.5.1.1 5.5.1.7 5.5.1.11 5.4.4.4 5.3.1.15 5.3.1.4 5.3.1.5 5.3.1.3 5.3.1.12 5.3.1.7 5.3.1.9 5.3.1.26 5.3.1.8 5.1.3.24 5.1.3.11 5.1.3.3 5.1.3.15 5.1.3.21 5.1.3.23 5.1.1.18 5.1.1.19 5.1.1.16 5.1.1.15 5.1.3.14 5.1.3.9 5.1.3.8 5.1.1.1 5.1.1.13 5.1.1.2 5.1.1.14 5.1.1.12 5.1.1.7 5.1.1.5 5.1.1.3 5.1.1.17 5.1.1.9 5.1.1.8 5.1.1.4 5.1.99.6 5.1.99.5 5.1.1.10 5.1.99.3 5.1.99.1 5.1.2.2 5.1.1.6 5.1.99.4 5.1.3.18 5.1.3.13 5.1.3.7 5.1.3.2 5.1.3.6 5.1.3.25 5.1.3.16 5.1.3.26 5.1.3.5 5.1.3.20 5.1.3.4 5.1.3.27 5.1.3.22 5.1.3.1 5.1.3.10 5.1.3.12 5.1.99.2 5.1.2.1 5.1.2.3 5.1.3.19 5.1.3.17 5.1.2.4 5.1.2.6 5.1.2.5 5.2.1.1 5.2.1.2 5.2.1.4 5.2.1.9 5.2.1.10 5.99.1.1 5.4.3.8 5.4.3.6 5.4.3.11 5.4.3.10 5.4.3.7 5.4.3.9 5.4.3.2 5.4.99.58 5.4.3.4 5.4.3.5 5.4.3.3 5.4.1.1 5.4.99.9 5.5.1.4 5.4.99.12 5.3.99.10 5.2.1.12 5.2.1.14 5.3.3.7 5.2.1.6 5.3.3.9 5.3.3.4 5.3.3.8 5.3.3.14 5.2.1.5 5.3.3.1 5.3.3.5 5.5.1.19 5.3.3.2 5.3.3.11 5.3.3.6 5.4.99.4 5.4.99.13 5.4.99.2 5.4.99.1 5.3.3.3 5.4.99.14 5.4.4.1 5.4.99.18 5.2.1.8 H'I' J'

Fig. S3. Analysis of isomerase reactions on the basis of reaction centres. (A) Total number of isomerase reactions (1st column) and reaction centres (2nd column) across EC subclasses. Bars are coloured according to subclass. (B) Distribution of the number of isomerase reactions versus the number of reaction centres. (C) Distribution of the number of reaction centres per isomerase reaction in each EC subclass. The number of reactions belonging to each subclass is shown in brackets. Coloured boxes represent interquartile ranges. Error bars represent 1.5 times the interquartile range. Points beyond the error bars refer to outliers. Cluster analysis of isomerase reactions based on similarities by reaction centres. (D) Distribution of pairwise similarities. (E) Reaction centre similarity matrix. Blue-to-red scale represents increasing similarity, identical reactions have a similarity of 1 (red). Reactions are annotated in colours according to their EC subclass (top row). Ten clusters were identified (A' to J'). (F) Hierarchical clustering of isomerase reactions (rows) by reaction centres (columns). The blue scale represents the number of reaction centres in reactions. Reactions are annotated in colours according to their EC subclass (left-hand column). Ten clusters were identified (A' to J'). The thirty most common reaction centres were ordered left-to-right by increasing number. Outliers are annotated with an arrow (Table S3).

13 Fig. S4 A B D

Subclass D − Ribose 5 phosphate − CoA (R) − Methylmalonyl UDP − L arabinose D − Glucose 1 phosphate D − Ornithine UDP − glucuronate 3 − Phospho D glycerate − muconate − cis,cis 3 − Carboxy 5 − phosphate L − Ribulose D − Lysine Lycopene 2 − Phospho D glycerate Chorismate D − Mannose 6 phosphate (3S) − 3,6 Diaminohexanoate D − Xylulose 5 phosphate D − Ribulose Squalene beta − D Glucose 6 phosphate Methylitaconate L − Lysine L − Glutamate L − Phenylalanine 5 − phosphate D − Ribulose D − Fructose 6 − phosphate Prostaglandin H2 D − Glucose 6 phosphate − D glucose − 6 deoxy dTDP − 4 oxo diphosphate Geranylgeranyl (S) − 2,3 Epoxysqualene 5.5.1.3 5.1.99.3 5.1.99.5 5.1 5.1.1.4 5.1.1.8 1 5.3.3.12 5.2.1.8 5.3.1.6 5.2 5.3.1.27 0 5.3.1.29 5.4.2.7 5.3.1.28 5.3 5.3.1.8 5.3.1.26 5.3.1.9 5.1.3.15 5.4 5.4.2.8 5.4.2.5 5.4.2.2 5.4.2.6 5.5 5.5.1.4 5.4.2.10 5.1.3.3 5.3.1.7 5.3.1.12 5.99 5.3.2.7 5.3.1.5 5.3.1.15 5.3.1.3 5.3.1.4 5.3.1.20 5.3.1.25 5.3.1.14 5.4.4.2 5.4.99.5 5.3.3.17 5.5.1.2 5.5.1.5 5.5.1.1 A'' 5.5.1.11 5.5.1.7 5.3.3.4 5.4.99.14 5.2.1.10 5.3.99.9 5.3.99.8 5.5.1.20 5.2.1.6 5.3.3.9 5.3.99.6 5.3.99.5 5.3.99.4 5.3.99.3 5.3.99.2 5.4.2.12 5.4.2.11 5.3.1.1 5.4.2.4 5.1.3.22 5.3.1.13 5.1.3.1 5.1.3.4 5.4.2.9 5.5.1.12 5.5.1.14 5.5.1.13 C 5.5.1.16 5.5.1.15 5.5.1.22 5.5.1.8 5.3.3.2 5.1.1.15 5.3.1.23 5.4.4.1 5.4.4.3 5.3.2.5 5.1.1.16 5.4.1.1 5.1.1.19 1 5.1.1.10 5.4.3.10 5.1.1.13 5.4.3.11 5.1.1.6 5.1.1.1 5.4.3.6 5.1.1.18 5.99.1.4 5.1.1.2 5.1.1.9 5.3.2.1 5.4.3.3 5.1.2.2 5.1.1.7 5.4.3.4 5.3.99.7 5.4.99.58 5.5.1.10 5.1.1.5 E'' 5.4.3.2 5.99.1.1 5.1.1.12 5.5.1.19 5.4.3.5 5.4.3.8 5.5.1.18 5.1.1.3 5.2.1.14 5.4.3.9 5.4.99.1 5.3.3.11 5.4.3.7 0.8 5.4.99.38 5.1.2.4 5.1.2.1 5.4.99.48 5.3.1.22 5.4.99.53 5.1.2.6 5.3.1.17 5.4.99.51 5.3.2.2 5.1.2.5 5.4.99.32 5.4.99.3 5.4.99.31 5.2.1.1 5.3.3.7 5.4.99.7 5.4.99.4 5.4.99.47 5.3.3.6 5.2.1.13 5.4.99.56 5.2.1.12 5.4.99.33 B'' 5.4.99.37 5.4.99.17 5.4.99.8 5.3.3.14 5.4.99.57 5.2.1.9 5.4.4.4 5.4.99.46 D'' 5.4.4.5 0.6 5.4.99.41 5.4.4.6 5.3.3.13 5.4.99.52 5.2.1.5 5.4.99.54 5.2.1.2 5.2.1.4 5.4.99.36 5.3.3.10 5.4.99.34 5.3.2.6 5.3.2.8 5.4.99.39 5.3.99.10 5.4.99.40 5.4.99.60 5.4.99.61 5.4.99.55 5.4.99.12 5.4.99.49 5.3.1.16 5.4.99.18 5.4.99.35 5.1.3.23 5.4.99.50 5.1.3.14 5.1.3.7 5.5.1.23 5.1.3.18 5.3.1.21 5.1.3.20 5.1.3.10 0.4 5.3.3.5 5.4.99.59 5.5.1.9 5.1.3.27 5.1.3.25 5.3.3.1 5.1.3.13 5.1.99.2 5.3.2.4 5.3.2.3 5.1.3.26 5.1.3.16 5.4.2.3 5.1.3.5 5.1.3.6 5.1.3.24 5.1.3.12 5.1.3.8 5.1.3.2 5.4.99.30 5.1.3.9 5.4.99.9 5.1.1.11 5.3.1.24 5.1.99.6 5.1.3.21 5.3.3.18 5.3.3.8 5.1.3.11 C'' 5.3.3.3 5.4.99.16 5.1.99.4 5.4.99.11 5.4.99.13 0.2 5.4.99.2 5.1.3.17 5.1.2.3 5.1.99.1 5.1.3.19 5.1.1.17 5.1.1.14 5.1.1.14 5.1.3.19 5.1.1.17 5.1.3.17 5.1.99.1 5.4.99.11 5.4.99.16 5.1.2.3 5.1.3.11 5.4.99.2 5.1.3.21 5.3.1.24 5.4.99.13 5.1.3.9 5.1.99.4 5.1.3.8 5.1.3.24 5.3.3.3 5.4.2.3 5.3.3.8 5.1.3.26 5.1.99.2 5.3.3.18 5.3.3.1 5.1.99.6 5.5.1.9 0 5.3.3.5 5.1.1.11 5.3.1.21 5.4.99.9 5.5.1.23 5.4.99.50 5.4.99.30 5.4.99.35 5.1.3.2 C'' 5.4.99.49 5.4.99.55 5.1.3.12 5.4.99.40 5.1.3.6 5.4.99.39 5.4.99.34 5.1.3.5 5.4.99.36 5.1.3.16 5.4.99.54 5.4.99.52 5.3.2.3 5.4.99.41 5.3.2.4 5.4.99.46 5.4.99.57 5.1.3.13 5.4.99.8 5.1.3.25 5.4.99.33 5.4.99.56 5.1.3.27 5.4.99.47 5.4.99.7 5.4.99.59 5.4.99.31 5.1.3.10 B'' 5.4.99.32 5.4.99.51 5.1.3.20 5.4.99.53 5.1.3.18 5.4.99.48 5.4.99.38 5.1.3.7 5.3.3.11 5.1.3.14 5.2.1.14 5.5.1.18 5.1.3.23 5.5.1.19 5.4.99.18 5.99.1.1 5.5.1.10 5.3.1.16 5.3.99.7 5.4.99.12 5.1.2.2 5.3.2.1 5.4.99.61 5.99.1.4 5.4.99.60 5.4.3.6 5.4.3.11 5.3.99.10 5.4.3.10 5.3.2.8 5.4.1.1 5.3.2.5 5.3.2.6 5.3.1.23 5.3.3.10 5.3.3.2 5.5.1.8 5.2.1.4 5.5.1.22 5.2.1.2 5.5.1.15 5.5.1.16 5.2.1.5 5.5.1.13 5.3.3.13 5.5.1.14 5.5.1.12 5.4.4.6 5.4.2.9 5.4.4.5 5.1.3.4 5.1.3.1 5.4.4.4 5.3.1.13 5.2.1.9 5.1.3.22 5.4.2.4 5.3.3.14 5.3.1.1 5.4.99.17 5.4.2.11 5.4.2.12 5.4.99.37 5.3.99.2 5.2.1.12 5.3.99.3 5.3.99.4 5.2.1.13 D'' 5.3.99.5 5.3.3.6 5.3.99.6 5.3.3.9 5.4.99.4 5.2.1.6 5.5.1.20 5.3.3.7 5.3.99.8 5.2.1.1 5.3.99.9 5.2.1.10 5.4.99.3 5.4.99.14 5.1.2.5 5.3.3.4 5.5.1.7 5.3.2.2 5.5.1.11 5.3.1.17 5.5.1.1 5.5.1.5 5.1.2.6 5.5.1.2 5.3.1.22 5.3.3.17 5.4.99.5 5.1.2.1 5.4.4.2 5.1.2.4 A'' 5.3.1.14 5.3.1.25 5.4.3.7 5.3.1.20 5.4.99.1 5.3.1.4 5.3.1.3 5.4.3.9 5.3.1.15 5.1.1.3 5.3.1.5 5.3.2.7 5.4.3.8 5.3.1.12 5.4.3.5 5.3.1.7 5.1.3.3 5.1.1.12 5.4.2.10 5.4.3.2 5.5.1.4 5.4.2.6 5.1.1.5 5.4.2.2 5.4.99.58 5.4.2.5 5.4.2.8 5.4.3.4 5.1.3.15 5.1.1.7 5.3.1.9 5.3.1.26 5.4.3.3 5.3.1.8 5.1.1.9 5.3.1.28 E'' 5.4.2.7 5.1.1.2 5.3.1.29 5.1.1.18 5.3.1.27 5.3.1.6 5.1.1.1 5.2.1.8 5.1.1.6 5.3.3.12 5.1.1.8 5.1.1.13 5.1.1.4 5.1.1.10 5.1.99.5 5.1.99.3 5.1.1.19 5.5.1.3 5.1.1.15 5.4.4.1 5.4.4.3 5.1.1.16 5.1.1.19 5.1.1.10 5.1.1.13 5.1.1.6 5.1.1.1 5.1.1.18 5.1.1.2 5.1.1.9 5.4.3.3 5.1.1.7 5.4.3.4 5.4.99.58 5.1.1.5 5.4.3.2 5.1.1.12 5.4.3.5 5.4.3.8 5.1.1.3 5.4.3.9 5.4.99.1 5.4.3.7 5.1.2.4 5.1.2.1 5.3.1.22 5.1.2.6 5.3.1.17 5.3.2.2 5.1.2.5 5.4.99.3 5.2.1.1 5.3.3.7 5.4.99.4 5.3.3.6 5.2.1.13 5.2.1.12 5.4.99.37 5.4.99.17 5.3.3.14 5.2.1.9 5.4.4.4 5.4.4.5 5.4.4.6 5.3.3.13 5.2.1.5 5.2.1.2 5.2.1.4 5.3.3.10 5.3.2.6 5.3.2.8 5.3.99.10 5.4.99.60 5.4.99.61 5.4.99.12 5.3.1.16 5.4.99.18 5.1.3.23 5.1.3.14 5.1.3.7 5.1.3.18 5.1.3.20 5.1.3.10 5.4.99.59 5.1.3.27 5.1.3.25 5.1.3.13 5.3.2.4 5.3.2.3 5.1.3.16 5.1.3.5 5.1.3.6 5.1.3.12 5.1.3.2 5.4.99.30 5.4.99.9 5.1.1.11 5.1.99.6 5.3.3.18 5.3.3.8 5.3.3.3 5.1.99.4 5.4.99.13 5.4.99.2 5.1.2.3 5.1.99.1 5.1.1.17 5.1.1.14 5.1.3.19 5.1.3.17 5.4.99.11 5.4.99.16 5.1.3.11 5.1.3.21 5.3.1.24 5.1.3.9 5.1.3.8 5.1.3.24 5.4.2.3 5.1.3.26 5.1.99.2 5.3.3.1 5.5.1.9 5.3.3.5 5.3.1.21 5.5.1.23 5.4.99.50 5.4.99.35 5.4.99.49 5.4.99.55 5.4.99.40 5.4.99.39 5.4.99.34 5.4.99.36 5.4.99.54 5.4.99.52 5.4.99.41 5.4.99.46 5.4.99.57 5.4.99.8 5.4.99.33 5.4.99.56 5.4.99.47 5.4.99.7 5.4.99.31 5.4.99.32 5.4.99.51 5.4.99.53 5.4.99.48 5.4.99.38 5.3.3.11 5.2.1.14 5.5.1.18 5.5.1.19 5.99.1.1 5.5.1.10 5.3.99.7 5.1.2.2 5.3.2.1 5.99.1.4 5.4.3.6 5.4.3.11 5.4.3.10 5.4.1.1 5.3.2.5 5.3.1.23 5.3.3.2 5.5.1.8 5.5.1.22 5.5.1.15 5.5.1.16 5.5.1.13 5.5.1.14 5.5.1.12 5.4.2.9 5.1.3.4 5.1.3.1 5.3.1.13 5.1.3.22 5.4.2.4 5.3.1.1 5.4.2.11 5.4.2.12 5.3.99.2 5.3.99.3 5.3.99.4 5.3.99.5 5.3.99.6 5.3.3.9 5.2.1.6 5.5.1.20 5.3.99.8 5.3.99.9 5.2.1.10 5.4.99.14 5.3.3.4 5.5.1.7 5.5.1.11 5.5.1.1 5.5.1.5 5.5.1.2 5.3.3.17 5.4.99.5 5.4.4.2 5.3.1.14 5.3.1.25 5.3.1.20 5.3.1.4 5.3.1.3 5.3.1.15 5.3.1.5 5.3.2.7 5.3.1.12 5.3.1.7 5.1.3.3 5.4.2.10 5.5.1.4 5.4.2.6 5.4.2.2 5.4.2.5 5.4.2.8 5.1.3.15 5.3.1.9 5.3.1.26 5.3.1.8 5.3.1.28 5.4.2.7 5.3.1.29 5.3.1.27 5.3.1.6 5.2.1.8 5.3.3.12 5.1.1.8 5.1.1.4 5.1.99.5 5.1.99.3 5.5.1.3 5.1.1.16 5.4.4.3 5.4.4.1 5.1.1.15

Fig. S4. Analysis of isomerase reactions on the basis of substrates and products. (A) Total number of isomerase reactions (1st column) and substrates and products (2nd column) across EC subclasses. Bars are coloured according to subclass. Cluster analysis of isomerase reactions based on similarities by substrates and products. (B) Distribution of pairwise similarities. (C) Substrates and products similarity matrix. Blue-to-red scale represents increasing similarity, identical reactions have a similarity of 1 (red). Reactions are annotated in colours according to their EC subclass (top row). Five clusters were identified (A'' to E''). (D) Hierarchical clustering of isomerase reactions (rows) by substrates and products (columns). Reactions are annotated in colours according to their EC subclass (left-hand column). Five clusters were identified (A'' to E''). The thirty most common substrates and products were ordered left-to-right by increasing number.

14 Fig. S5 A B

C D Bond changes Reaction centres Bond changes Substrates and products

Subclass A Subclass A 5.1 B A' 5.1 B 5.2 5.2 5.3 5.3 A'' 5.4 B' 5.4 5.5 5.5 5.99 C 5.99 C C'

D' B'' D D E' E E C''

F' D'' F F G' E'' H' I' J' E F Clusters by reaction centres Clusters by substrates and products

A' B' C' D' E' F' G' H' I' J' A'' B'' C'' D'' E'' A 0 0 0 0 0 0 11 0 0 0 A 9 0 2 0 0 B 4 5 0 0 0 0 0 0 0 0 B 2 1 0 6 0 C 33 0 0 0 36 9 0 0 3 1 C 33 11 15 12 11 D 0 0 0 0 20 0 1 1 0 0 D 12 2 4 4 0 E 1 0 0 0 0 37 0 0 0 0 E 9 27 0 2 0 F 0 0 56 1 0 0 0 0 0 0 F 9 2 28 4 14 Clusters by bond changes Clusters by bond changes

Fig. S5. Comparative analysis of isomerase reactions on the basis of bond changes, reaction centres and substrates and products. Comparison of similarity distributions of isomerase reactions as calculated by (A) bond changes versus reaction centres and (B) bond changes versus substrates and products (B). Each point represents a pair of isomerase reactions. Comparison of clusters of isomerase reactions using tanglegrams as calculated by (C) bond changes versus reaction centres and (D) bond changes versus substrates and products. Tanglegrams link reactions, which are coloured according to EC subclass, from different clustering trees (Materials and methods). Comparison of clusters of isomerase reactions using contingency tables as calculated by (E) bond changes versus reaction centres and (F) bond changes versus substrates and products. Contingency tables cross tabulate the number of reactions shared between the clusters obtained from different clustering trees.

15 Fig. S6

A − 3 hydroxybutyl 2 − azanylidene 2 − methylpropyl (2 − aminobutanoyl)oxidanyl O=P(O)(O[P])O[P] *C([C])[C] *C1N[C][N]C1=O [C]C([N])[N] [P]O[P] [C]NC1N[C][N]C1=O [c]c([c])C(O)C(=O)[O] phosphatediyl group O=C([O])C(C(=O)[S])C [C]C([O])C(N)C(=O)[O] [O]P(=O)([O])[O] *C([C])C(O[C])C(=O)[O] *C([C])[N] O=C([O])C(N)C[O] O=C([O])C1N[C][C]C1 [C]C([n])[O] [C]NC(C([C])[O])C([O])[O] [c]n([c])C1O[C][C]C1[O] [C]C([O])C(O)C[O] (1,2 − dihydroxypropoxy)methyl [C]C([O])[O] − 4 oxopentyl 2,3 − dihydroxy [C]C([O])C(O)C([C])[O] − 4 oxobutyl 3 − amino 4 hydroxy 2 − azanylidenepropyl 2 − hydroxypropyl carbon atom UDP − D galacturonate L − Proline D − Serine meso − 2,6 Diaminoheptanedioate − undecaprenol − diphospho ditrans,octacis N − Acetyl alpha D galactosaminyl D − Glucosyl mannose L − Threonine UDP − N acetyl D galactosamine [Protein] − L serine N − Acetyl alpha neuraminate D − glucuronate Heparosan − N sulfate − CoA (S) − Methylmalonyl beta − Maltose alpha − D Glucose N − Acetyl D glucosaminyldiphosphoundecaprenol O − Ureido D serine D − Amino acid UDP − D xylose GDP − L galactose (S) − Mandelate N − Acyl D mannosamine 6 phosphate 5 − phosphate D − Ribulose Isopenicillin N Chondroitin (R) − Lactate 5 − phosphate L − Ribulose D − Xylulose 5 phosphate UDP − glucuronate UDP − N acetyl alpha D glucosamine − D glucose − 6 deoxy dTDP − 4 oxo

5.1.1.11 6 5.1.1.4 5.1.99.6 5.1.1.8 1 5.1.99.3 5.1.1.15 5.1.2.2 5.1.2.5 0 5.1.99.5 5.1.2.6 5.1.1.10 5 5.1.2.1 5.1.99.1 5.1.2.4 5.1.1.13 5.1.1.12 Subsubclass 5.1.1.2 5.1.1.3 5.1.1.14 5.1.1.7 5.1.1 5.1.1.12 4 5.1.1.5 5.1.1.7 5.1.1.18 5.1.2 5.1.1.5 5.1.1.1 5.1.1.3 5.1.1.6 5.1.3 5.1.1.17 5.1.1.13 5.1.99 5.1.1.9 3 5.1.1.10 5.1.3.23 5.1.1.9 5.1.1.18 5.1.1.2 5.1.1.19 5.1.3.1 5.1.1.16 2 5.1.3.22 5.1.1.15 5.1.3.4 5.1.3.14 5.1.1.19 5.1.3.9 5.1.2.2 5.1.3.8 5.1.1.16 5.1.1.1 1 5.1.99.2 5.1.1.8 5.1.99.5 5.1.1.4 5.1.99.3 5.1.3.24 5.1.3.3 5.1.3.11 5.1.3.15 5.1.3.3 0 5.1.3.8 5.1.3.15 5.1.3.9 5.1.3.21 5.1.99.1 5.1.1.6 5.1.2.3 5.1.99.4 5.1.99.4 5.1.3.18 5.1.99.6 5.1.3.13 5.1.3.20 5.1.3.7 5.1.3.18 5.1.3.2 5.1.3.2 5.1.3.6 5.1.3.12 5.1.3.25 5.1.3.6 5.1.3.16 5.1.3.16 5.1.3.26 5.1.3.5 5.1.3.5 5.1.3.7 5.1.3.20 5.1.3.14 5.1.3.4 5.1.3.25 5.1.3.27 5.1.3.13 5.1.3.22 5.1.3.27 5.1.3.1 5.1.3.23 5.1.3.10 5.1.3.10 5.1.3.12 5.1.1.11 5.1.99.2 5.1.3.26 5.1.2.1 5.1.3.17 5.1.2.3 5.1.3.19 5.1.3.19 5.1.3.21 5.1.3.17 5.1.3.11 5.1.2.4 5.1.3.24 5.1.2.6 5.1.1.17 5.1.2.5 5.1.1.14

B 3 − Oxo delta5 steroid Methylitaconate D − Mannose 6 phosphate − 1 en 3 ulose − D glycero hex − 4 deoxy 1,5 − Anhydro − CoA Vinylacetyl phosphate − 5 yl)ethyl − 4 methylthiazol 2 − (2 Carboxy 5alpha − Cholest 8 en 3beta ol Phenylacetaldehyde D − Fructuronate Neoxanthin Piperitenone − dTDP D glucose − 3 oxo 3,6 − Dideoxy − 1,3 diene 1 carboxyate − 6 Amino 5 hydroxycyclohexane (5S,6S) D − Ribose 5 phosphate − 5 acetate 2 − Oxo 2,3 dihydrofuran − L galactose 6 − Deoxy diphosphate Dimethylallyl (5Z,8Z,11Z,14Z,17Z) − Icosapentaenoic acid D − Ribose − 5 amino 1 (5 phospho D ribosyl)N − (5 Phospho D 1 ribulosylformimino) − 4 imidazolecarboxamide 5 − (5 Phospho D ribosylaminoformimino) − 1 (5 phosphoribosyl)− 4 carboxamide − imidazole Prostaglandin I2 − CoA − Dodecenoyl 2 − trans D − Xylulose Violaxanthin − D glucose − 6 deoxy dTDP − 4 oxo D − Ribulose 5 − phosphate D − Ribulose D − Fructose 6 − phosphate Prostaglandin H2 C − O C%C*C@C C − O − P*O=P C%C*C=C C%C O%O C(E/Z) C%O*C=O C%C*C%C C − C*C=C C − O*C=O C%O H − O C(R/S) C − H − 1 en ylidene 2 − methylprop − 2 en 1 yl 2 − hydroxyprop 2 − oxoethyl [C]C1[C][C]C([C])([O])O1 [C]C1O[C]C([O])C1O pent − 3 en 1 yl [C]=C([C])[O] − 4 oxopentyl 2,3 − dihydroxy [C]C([O])C(=O)C[O] prop − 1 en ylidene 2 − (1 hydroxyethoxy)propyl − 2 oxopropyl 3 − hydroxy 2 − methylpropyl − 2 en 1 yl 2 − methylprop [C]C([O])([O])CO [C]C([C])([O])[O] [O]CC1(O)O[C][C]C1[O] (1,2 − dihydroxypropoxy)methyl [C]C([O])C(O)C([O])[O] [C]C([O])[O] propyl methoxymethyl prop − 2 en 1 yl 2 − hydroxyethyl hydroxymethyl 2 − oxopropyl oxomethylidene 2 − hydroxypropyl atom oxygen carbon atom 5.3.1.13 4 5.3.3.12 14 5.3.1.7 5.3.1.17 5.3.99.10 5.3.1.12 1 5.3.1.21 5.3.2.5 5.3.1.20 5.3.1.1 5.3.99.7 5.3.1.5 0 5.3.1.22 5.3.99.9 12 5.3.1.15 5.3.3.12 5.3.99.5 5.3.1.3 5.3.2.2 5.3.99.4 5.3.1.4 5.3.1.27 3 5.3.99.2 5.3.2.7 Subsubclass 5.3.1.16 5.3.99.3 10 5.3.1.25 5.3.1.23 5.3.2.1 5.3.1.14 5.3.1 5.3.1.24 5.3.2.6 5.3.1.6 5.3.1.25 5.3.2.8 5.3.1.27 5.3.2 5.3.1.14 5.3.1.20 8 5.3.1.29 5.3.1.6 5.3.1.15 5.3.1.8 5.3.3 5.3.1.28 2 5.3.1.4 5.3.1.26 5.3.2.3 5.3.1.5 5.3.1.9 5.3.99 5.3.2.4 5.3.1.3 6 5.3.1.28 5.3.2.5 5.3.1.12 5.3.1.23 5.3.1.12 5.3.1.7 5.3.1.13 5.3.1.15 5.3.1.9 5.3.1.1 5.3.1.5 5.3.1.26 4 5.3.2.5 5.3.1.26 1 5.3.1.8 5.3.1.24 5.3.1.8 5.3.2.7 5.3.3.2 5.3.1.9 5.3.2.2 5.3.99.5 5.3.1.3 5.3.1.1 2 5.3.99.4 5.3.1.7 5.3.1.17 5.3.99.3 5.3.1.4 5.3.1.13 5.3.99.2 5.3.99.7 5.3.1.21 5.3.3.9 5.3.99.9 0 5.3.1.22 0 5.3.99.6 5.3.1.29 5.3.1.29 5.3.99.9 5.3.1.20 5.3.1.27 5.3.99.8 5.3.99.3 5.3.2.4 5.3.3.5 5.3.99.2 5.3.2.3 5.3.1.21 5.3.99.4 5.3.1.28 5.3.3.3 5.3.3.4 5.3.1.14 5.3.3.8 5.3.3.9 5.3.1.25 5.3.3.18 5.3.3.5 5.3.1.16 5.3.1.16 5.3.3.1 5.3.1.24 5.3.2.3 5.3.3.18 5.3.1.23 5.3.2.4 5.3.2.7 5.3.1.6 5.3.2.8 5.3.3.17 5.3.99.8 5.3.2.6 5.3.3.3 5.3.3.10 5.3.3.10 5.3.3.2 5.3.3.17 5.3.3.7 5.3.3.6 5.3.99.6 5.3.3.6 5.3.3.14 5.3.3.13 5.3.2.2 5.3.3.8 5.3.3.18 5.3.1.17 5.3.3.11 5.3.3.3 5.3.1.22 5.3.99.10 5.3.3.9 5.3.3.13 5.3.3.10 5.3.3.4 5.3.3.1 5.3.3.13 5.3.3.8 5.3.2.1 5.3.2.1 5.3.3.14 5.3.99.7 5.3.2.6 5.3.3.7 5.3.3.11 5.3.2.8 5.3.3.2 5.3.99.10 5.3.99.6 5.3.3.11 5.3.3.4 5.3.99.8 5.3.3.6 5.3.3.12 5.3.99.5 5.3.3.1 5.3.3.14 5.3.3.7 5.3.3.5 5.3.3.17

C C(E/Z) C − P O − N − O C%N*C%N C − O*C=O C=C C%C*C%C C=O H − N C%C*C − C C − O O − P C − N C − C*C=C C%C*C=C C%O C%C H − O C − C − H C(R/S) 2 − hydroxyethyl − 4 en 1 yl 4 − methylpent 2,2 − dimethylpentyl − 3,3,4 trimethylpentyl 2 − hydroxy pent − 4 en 1 yl − 3 (propan 2 yl)pentyl 2,3 − dimethyl azanyl − 2,2 dimethylpentyl 3 − hydroxy 3 − tert− 2,2 dimethylpentyl − butyl 2,2 − dimethylpropyl − 2 yl)methyl (2 − methyloxiran − 2 yl)methyl (3,3 − dimethyloxiran [C]1[C]O1 − 2 ylmethyl oxiran − 2 yl)methyl (2,3 − dimethyloxiran − 2 yl)ethyl 2 − (3,3 dimethyloxiran − 3 en 1 yl 4 − methylpent − 3 en 1 yl 3 − methylpent dimethylpropyl prop − 2 en 1 yl prop − 1 en ylidene − 1 en ylidene 2 − methylprop − 2 en 1 yl 2 − methylprop 2 − methylpropyl 2 − hydroxypropyl ethyl hydroxymethyl propyl atom oxygen carbon atom dTDP − D fucose Hydroxylaminobenzene delta − Amyrin D − Mannose 6 phosphate Achilleol B alpha,alpha − Trehalose Cycloartenol UDP − L arabinofuranose Precorrin 8X Tirucalla − 7,24 dien 3beta ol D − Ribose 5 phosphate D − Glucosamine 6 phosphate 2,3 − Bisphospho D glycerate − 1 (5 phospho D ribosyl)imidazole 5 − Carboxyamino L − beta Phenylalanine acid − 2 oxobutanoic − 3 methyl 3 − Hydroxy Diploptene 2 − Methyleneglutarate (3S) − 3,6 Diaminohexanoate D − Glucose 6 phosphate 2 − Phospho D glycerate L − Glutamate Squalene L − Lysine 8(R) − HPODE D − Glucose 1 phosphate L − Phenylalanine 3 − Phospho D glycerate Chorismate (S) − 2,3 Epoxysqualene 5.4.4.2 5.4.2.9 5.4.99.3 5.4.99.5 5.4.99.3 40 5.4.99.4 1 5.4.99.61 5.4.4.2 5.4.99.58 5.4.99.60 5.4.99.5 5.4.3.4 0 5.4.99.11 5.4.99.38 5.4.3.2 5.4.99.16 5.4.99.9 5.4.3.3 5.4.4.6 15 5.4.4.4 5.4.3.9 5.4.4.5 5.4.1.1 5.4.99.1 Subsubclass 5.4.99.9 5.4.99.1 30 5.4.3.7 5.4.99.40 5.4.99.2 5.4.3.8 5.4.1 5.4.99.46 5.4.99.4 5.4.3.5 5.4.99.55 5.4.99.13 5.4.4.6 5.4.2 5.4.99.35 5.4.99.14 5.4.4.5 5.4.3 5.4.99.39 10 5.4.99.59 5.4.4.4 5.4.99.57 5.4.99.30 20 5.4.2.12 5.4.4 5.4.99.33 5.4.99.16 5.4.2.11 5.4.99.36 5.4.99.11 5.4.2.4 5.4.99 5.4.99.49 5.4.4.6 5.4.2.9 5.4.99.48 5.4.4.5 5.4.3.10 5.4.99.50 5.4.3.2 5.4.3.11 5.4.99.52 5.4.3.9 5.4.3.6 5.4.99.54 5 5.4.3.7 10 5.4.4.2 5.4.99.51 5.4.3.10 5.4.99.5 5.4.99.47 5.4.3.11 5.4.99.57 5.4.99.34 5.4.3.6 5.4.99.46 5.4.99.53 5.4.3.3 5.4.99.7 5.4.99.56 5.4.3.5 5.4.99.47 5.4.99.7 5.4.3.4 5.4.99.56 5.4.99.41 0 5.4.99.58 0 5.4.99.33 5.4.99.8 5.4.3.8 5.4.99.8 5.4.99.31 5.4.99.12 5.4.99.32 5.4.99.17 5.4.99.33 5.4.99.31 5.4.99.37 5.4.99.47 5.4.99.48 5.4.99.32 5.4.99.56 5.4.99.38 5.4.3.6 5.4.99.8 5.4.99.52 5.4.3.9 5.4.99.7 5.4.99.54 5.4.3.5 5.4.99.32 5.4.99.36 5.4.3.4 5.4.99.17 5.4.99.34 5.4.3.3 5.4.99.37 5.4.99.39 5.4.3.10 5.4.99.41 5.4.99.40 5.4.3.11 5.4.99.53 5.4.99.55 5.4.3.7 5.4.99.31 5.4.99.49 5.4.3.2 5.4.99.55 5.4.99.35 5.4.99.58 5.4.99.35 5.4.99.50 5.4.3.8 5.4.99.36 5.4.99.41 5.4.99.12 5.4.99.40 5.4.99.53 5.4.99.1 5.4.99.39 5.4.99.51 5.4.99.2 5.4.99.34 5.4.99.17 5.4.99.13 5.4.99.50 5.4.99.37 5.4.1.1 5.4.99.49 5.4.2.8 5.4.99.14 5.4.99.51 5.4.2.5 5.4.99.4 5.4.99.57 5.4.2.2 5.4.99.38 5.4.99.46 5.4.2.6 5.4.99.18 5.4.99.52 5.4.2.10 5.4.99.59 5.4.99.54 5.4.2.7 5.4.99.30 5.4.99.48 5.4.2.3 5.4.4.3 5.4.99.61 5.4.99.11 5.4.4.1 5.4.99.60 5.4.99.16 5.4.99.3 5.4.2.12 5.4.99.9 5.4.2.11 5.4.2.11 5.4.99.30 5.4.2.4 5.4.2.4 5.4.99.59 5.4.2.12 5.4.2.3 5.4.99.13 5.4.2.10 5.4.2.8 5.4.99.2 5.4.2.5 5.4.2.2 5.4.99.12 5.4.2.8 5.4.2.5 5.4.99.18 5.4.2.2 5.4.2.6 5.4.99.61 5.4.2.3 5.4.2.7 5.4.99.60 5.4.2.6 5.4.2.10 5.4.99.14 5.4.2.7 5.4.4.3 5.4.1.1 5.4.2.9 5.4.4.1 5.4.4.3 5.4.4.4 5.4.99.18 5.4.4.1

Fig. S6. Analysis of racemases and epimerase reactions (EC 5.1), intramolecular oxidoreductase reactions (EC 5.3) and intramolecular transferase reactions (EC 5.4). (A) Hierarchical clustering of racemase and epimerase reactions (rows) by reaction centres (left) and substrates and products (right). The blue scale represents the number of chemical attributes in reactions. Reactions are annotated in colours according to their EC sub-subclass (left-hand column). The thirty most common chemical attributes were ordered left-to-right by increasing number. Reactions discussed in SI Appendix are marked with arrows. (B) Hierarchical clustering of intramolecular oxidoreductase reactions (rows) by bond changes (left), reaction centres (middle) and substrates and products (right). (C) Hierarchical clustering of intramolecular transferase reactions (rows) by bond changes (left), reaction centres (middle) and substrates and products (right). Oxidosqualene cyclisations are highlighted in purple boxes.

16 Fig. S7

Reactions Bond changes Reaction centres Substrates and products

Alanine racemase EC 5.1.1.1 Types Similarities Types (level 2) Similarities Types Similarities O O

O O L-alanine CH3 CH3 HO HO C(R/S) from C(R/S): O O D-alanine

N N NH2 NH2 L-alanine D-alanine 1.0 0.43 0.41

Lysine racemase EC 5.1.1.5

O O O O L-lysine NH NH 2 2 C(R/S) 0.13 from C(R/S): O O 0.19 0.53 HO HO D-lysine N N

NH2 NH2 L-lysine D-lysine 0.21 0.8 0.13 O O from C(R/S): Methylornithine synthase EC 5.4.99.58 O O

O O N N L-lysine NH2 HO HO NH C(R/S), C-C (2x) from C-C: 2 (2R,3R)-3-methylornithine N NH2 NH2

L-lysine (2R,3R)-3-methylornithine from C-C:

N

Fig. S7. Obtaining bond changes, reaction centres and structures of substrates and products from three isomerase reactions belonging to two different EC subclasses: alanine racemisation (EC 5.1.1.1), lysine racemisation (EC 5.1.1.5) and methylornithine synthesis (EC 5.4.99.58). C(R/S) indicates carbon chiral inversion and arrows represent similarity scores as calculated using EC-BLAST. To simplify the example, only reaction centres at level 2 are shown (substructures consisting of substrate and product bond changing atoms extended by two covalent bonds around them).

17 Fig. S8 CATH domains A 3.10.20.90 3.10.50.40 3.10.129.10 3.10.180.10 3.10.290.10 3.10.310.10 3.10.320.10 3.10.450.50 3.10.580.10 3.20.14.10 3.20.20.10 3.20.20.60 3.20.20.70 3.20.20.80 3.20.20.110 3.20.20.120 3.20.20.140 3.20.20.150 3.20.20.440 3.30.65.10 3.30.66.10 3.30.70.100 3.30.70.150 3.30.70.260 3.30.70.330 3.30.70.580 3.30.70.1050 3.30.70.1250 3.30.70.1560 3.30.200.20 3.30.300.30 3.30.310.50 3.30.360.10 3.30.390.10 3.30.410.10 3.30.429.10 3.30.500.10 3.30.565.10 3.30.1330.40 3.30.1360.40 3.30.1540.10 3.30.1590.10 3.30.2340.10 3.30.2350.10 3.40.30.10 3.40.50.280 3.40.50.300 3.40.50.720 3.40.50.980 3.40.50.1000 3.40.50.1070 3.40.50.1100 3.40.50.1240 3.40.50.1260 3.40.50.1360 3.40.50.1860 3.40.50.2000 3.40.50.2300 3.40.50.7700 3.40.50.10230 3.40.50.10260 3.40.50.10470 3.40.50.10490 3.40.50.10860 3.40.120.10 3.40.225.10 3.40.275.10 3.40.640.10 3.40.720.10 3.40.980.10 3.40.1360.10 3.40.1400.10 3.40.1450.10 3.40.1650.10 3.50.50.60 3.50.70.10 3.60.21.10 3.60.120.10 3.90.15.10 3.90.25.10 3.90.79.10 3.90.199.10 3.90.226.10 3.90.400.10 3.90.850.10 3.90.1150.10 2.20.25.10 2.20.70.10 2.30.29.30 2.30.38.10 2.30.130.10 2.40.37.10 2.40.100.10 2.40.110.10 2.40.128.20 2.40.480.10 2.60.40.10 2.60.40.790 2.60.40.1180 2.60.120.10 2.60.120.340 2.60.120.520 2.70.20.10 2.70.98.10 2.120.10.90 2.130.10.10 2.170.11.10 2.170.16.10 1.10.10.41 1.10.10.470 1.10.12.10 1.10.40.30 1.10.150.200 1.10.150.240 1.10.268.10 1.10.274.20 1.10.275.10 1.10.290.10 1.10.375.10 1.10.510.10 1.10.590.10 1.10.600.10 1.10.630.10 1.10.890.20 1.10.1040.10 1.10.1620.10 1.10.2020.10 1.10.3140.10 1.20.59.10 1.20.80.10 1.20.120.290 1.20.120.420 1.20.120.450 1.20.120.550 1.20.140.10 1.20.200.10 1.20.1050.10 1.25.40.10 1.50.10.10 1.50.10.20 1.50.10.130 5.1.1.1 3 5.1.1.3 1 5.1.1.4 1 5.1.1.5 2 5.1.1.7 1 5.1.1.8 1 5.1.1.10 2 5.1.1.11 3 5.1.1.13 1 5.1.1.15 2 5.1.1.18 1 5.1.1.20 2 5.1.2.2 2 5.1.2.3 2 5.1.3.1 1 5.1.3.2 2 5.1.3.3 1 5.1.3.4 1 5.1.3.7 1 5.1.3.8 1 5.1.3.9 1 5.1.3.10 1 5.1.3.11 1 5.1.3.13 1 5.1.3.14 1 5.1.3.15 1 5.1.3.18 1 5.1.3.20 2 5.1.3.22 1 5.1.3.27 1 5.1.3.29 1 5.1.99.1 1 5.1.99.4 1 5.1.99.6 1 5.2.1.2 1 Number of CATH domains per EC number 5.2.1.4 3 5.2.1.8 14 5.3.1.1 4 5.3.1.3 3 5.3.1.5 1 5.3.1.6 3 5.3.1.8 3 5.3.1.9 3 5.3.1.12 2 5.3.1.13 2 5.3.1.14 1 5.3.1.16 1 5.3.1.17 2 5.3.1.22 1 5.3.1.23 2 5.3.1.24 1 5.3.1.25 3 5.3.1.26 1 5.3.1.27 1 5.3.1.28 1 5.3.1.29 2 5.3.1.31 1 5.3.2.1 1 5.3.2.2 1 5.3.2.3 1 5.3.2.5 2 5.3.2.6 1 5.3.3.1 3 5.3.3.2 2 5.3.3.3 3 5.3.3.6 1 5.3.3.8 4 5.3.3.10 2 5.3.3.12 3 5.3.3.14 1 5.3.3.17 1 5.3.3.18 2 5.3.4.1 1

EC numbers 5.3.99.2 3 5.3.99.3 3 5.3.99.4 1 5.3.99.6 1 5.3.99.10 1 5.3.99.11 1 5.4.1.2 1 5.4.2.1 3 5.4.2.2 3 5.4.2.3 1 5.4.2.4 1 5.4.2.6 2 5.4.2.7 2 5.4.2.8 3 5.4.2.9 1 5.4.2.10 2 5.4.2.11 1 5.4.2.12 1 5.4.3.4 1 5.4.3.5 1 5.4.3.6 2 5.4.3.8 2 5.4.3.10 3 5.4.4.2 1 5.4.11.99 3 5.4.99.1 4 5.4.99.2 1 5.4.99.5 7 5.4.99.7 1 5.4.99.9 1 5.4.99.11 3 5.4.99.12 1 5.4.99.14 1 5.4.99.15 5 5.4.99.16 2 5.4.99.17 1 5.4.99.18 1 5.4.99.19 4 5.4.99.21 4 5.4.99.22 1 5.4.99.23 1 5.4.99.24 1 5.4.99.25 2 5.4.99.27 1 5.4.99.28 1 5.4.99.29 1 5.4.99.58 1 5.4.99.60 1 5.4.99.61 1 5.4.99.62 1 5.5.1.1 2 5.5.1.2 3 5.5.1.4 2 5.5.1.5 1 5.5.1.6 2 5.5.1.7 2 5.5.1.8 2 5.5.1.12 2 5.5.1.13 1 5.5.1.23 1 5.99.1.2 8 5.99.1.3 8 5.99.1.4 1 1 1 1 1 1 1 1 1 3 111121111111112111 3 3 1 4 2 3 1111121111214 6 1112111111112 5 1 2 1 2 2 1 8 5 1 5 1 5 1 1 1 1 1 1 1 3 1 1 2 1 1 4 1 5 1 5 1 1 1 1 1 1 1 8 5 3 110 1 3 2 1 3 1 1 2 1 1 1 3 1 2 5 1 3 1 2 2 3 1121211121211 3 4 1 2 Number of EC numbers per CATH domain

B CATH domain (third level) 3.10.20 3.10.50 3.10.129 3.10.180 3.10.290 3.10.310 3.10.320 3.10.450 3.10.580 3.20.14 3.20.20 3.30.65 3.30.66 3.30.70 3.30.200 3.30.300 3.30.310 3.30.360 3.30.390 3.30.410 3.30.429 3.30.500 3.30.565 3.30.1330 3.30.1360 3.30.1540 3.30.1590 3.30.2340 3.30.2350 3.40.30 3.40.50 3.40.120 3.40.225 3.40.275 3.40.640 3.40.720 3.40.980 3.40.1360 3.40.1400 3.40.1450 3.40.1650 3.50.50 3.50.70 3.60.21 3.60.120 3.90.15 3.90.25 3.90.79 3.90.199 3.90.226 3.90.400 3.90.850 3.90.1150 2.20.25 2.20.70 2.30.29 2.30.38 2.30.130 2.40.37 2.40.100 2.40.110 2.40.128 2.40.480 2.60.40 2.60.120 2.70.20 2.70.98 2.120.10 2.130.10 2.170.11 2.170.16 1.10.10 1.10.12 1.10.40 1.10.150 1.10.268 1.10.274 1.10.275 1.10.290 1.10.375 1.10.510 1.10.590 1.10.600 1.10.630 1.10.890 1.10.1040 1.10.1620 1.10.2020 1.10.3140 1.20.59 1.20.80 1.20.120 1.20.140 1.20.200 1.20.1050 1.25.40 1.50.10 5.1.1 5.1.2 5.1.3 5.1.99 5.2.1 5.3.1 5.3.2 5.3.3 5.3.4 5.3.99 5.4.1 5.4.2 5.4.3 5.4.4 5.4.99 5.5.1 EC sub-subclass 5.99.1

Fig. S8. The domain composition of all known isomerase 3D structures. (A) Rows refer to isomerase EC numbers and columns indicate CATH domains as available in the PDB. The different colours in each row represent unrelated enzymes with no domain in common, e.g. alanine racemase (EC 5.1.1.1) has emerged from two different evolutionary paths: in red, a two-domain protein architecture consisting of ornithine decarboxylase (CATH 2.40.37.10) and alanine racemase (CATH 3.20.20.10) domains, and in green, a structural domain that has not been named yet (CATH 3.40.50.2300). The row and column totals are given on the right and bottom sides of the plot. (B) Rows refer to isomerase EC sub-subclass whereas columns indicate CATH domains aggregated to the third level of the classification. A red square represents one or more domains involved in an EC number (Fig. 3A).

18 Fig. S9 A B H − O C − H C(R/S) C − O O − P H − N C − O < > C=O C − N H − S C − C=O C − S C − O(ring) C − < > C=C C − C(ring) < − > C C(ring) C − N(ring) < − > C N(ring) C − C(ring) O=O C(E/Z) O − S C − C(ring) < − > C=C H − O − P(ring) C − P S − Mo − O Mo − S(ring) O − < > O=O C − Cl O − S < > O=S 6.3 3.4 3.5 3.10 3.9 2.10 6.6 4.6 6.5 3.6 2.7 2.9 6.2 6.1 6.4 1.10 3.12 1.9 1 5.99 1.20 1.8 1.11 5 0.8 2.4 3.2 3.8 1.16 4 0.6 3.1 3.3 3.13 3 2.3 0.4 2.1 4.4 2 2.5 0.2 1.17 2.8 1.2 1 3.7 0 3.11 4.7 0 1.18 1.22 5.2 1.12 1.97 4.99 2.6 4.5 4.3 1.4 1.5 1.6 1.7 1.13 1.14 1.21 5.1 5.5 4.2 5.4 2.2 1.1 4.1 1.23 1.3 5.3 1.17 1.97 1.14 1.18 1.16 1.22 1.12 1.20 1.10 1.23 1.13 5.99 3.12 2.10 3.10 3.13 4.99 1.11 1.21 3.11 1.4 1.7 1.8 1.5 1.6 1.2 1.9 1.3 6.4 6.6 6.5 5.4 2.4 2.7 6.2 3.7 3.4 6.3 4.4 4.7 5.5 2.5 2.8 2.6 5.2 3.8 2.2 3.5 3.6 3.2 2.9 4.5 5.3 3.9 4.6 2.3 4.2 3.3 4.3 1.1 6.1 5.1 2.1 3.1 4.1

Fig. S9. The chemical neighbourhood of isomerases in the universe of enzyme reactions. Clustering of EC subclasses based on the number of bond changes. (A) Heat map representing similarity between subclasses according to a scale from 0 (no similarity) to 1 (identical frequencies of bond changes). (B) Panel indicating the normalised count of the 30 most common bond changes in subclasses. Arrows indicate isomerase EC subclasses.

19 Table S1. Overall statistics of the chemical attributes found in isomerase reactions. Column Types refers to the number of distinct types of chemical attributes. Column Pairs (possible) represent the maximum number of all possible combinations of pairs of isomerase reactions and chemical attributes (Types × 219). Column Pairs (observed) indicated the number of pairs of attributes and reactions detected in our dataset. Column Distinctive indicates the number and proportion of chemical attributes characteristic to an isomerase subclass. Chemical attribute Types Pairs (possible) Pairs (observed) Distinctive Bond changes 30 6570 746 (11.3%) 12 (40%) Reaction centres 595 139065 3067 (2.2%) 468 (79%) Substrates and 370 81030 442 (0.5%) 354 (96%) products

20 Table S2. Analysis of the clusters obtained by bond changes. The columns cluster, number of reactions and EC subclasses are self-explanatory. In EC subclasses, the most common subclass is underlined and the number of reactions belonging to each subclass is shown in brackets. The main bond changes of a cluster were considered as those present in at least 80% of the reactions belonging to the same cluster. An outlier in a cluster is a reaction from a different EC subclass than adjacent reactions in the same cluster1. Number of Main bond Outliers and Cluster EC subclasses reactions changes comments EC 5.1.1.11 is a EC 5.1 (1) and 5.4 A 11 H–O and O–P misannotated reaction. Pure (10) cluster EC 5.3.3.7 is a B 9 EC 5.2 (8) and 5.3 (1) C(E/Z) misannotated reaction. Pure cluster EC 5.2 (3), 5.3 (37), EC 5.2.1.5 is a C 82 5.4 (34), 5.5 (7) and C–H misannotated reaction. 5.99 (1) Mixed cluster EC 5.5.1.3 is a distinct EC 5.3 (18), 5.4 (1), C–H, O–H and C– D 22 reaction. Almost pure 5.5 (2) and 5.99 (1) O↔C=O cluster EC 5.3 (1), 5.4 (26) C–H, C–C(ring), C–C EC 5.4.99.38 is a distinct E 38 and 5.5 (11) and C–C(ring)↔C=C reaction. Mixed cluster F 57 EC 5.1 (57) C(R/S) No outliers. Pure cluster 1 Two main types of outliers were identified: first, outliers were defined as distinct if at least one of its bond changes is unique among the rest of bond changes from surrounding reactions. Conversely, an outlier was defined as misannotated if its bond changes are shared by at least two other neighbouring reactions of a different subclass. As an example, in cluster D we identified EC 5.5.1.3 as a distinct reaction because among other bond changes, H–O is present and C–H is absent in reactions EC 5.3.2.5, 5.3.1.13 and 5.3.1.27. On the other hand, EC 5.2.1.5 in cluster C was considered as a misannotated reaction because it shares the presence of all its bond changes C(E/Z), C–C↔C=C and C–H with reactions EC 5.3.3.8, 5.3.3.13 and 5.3.3.14.

21 Table S3. Analysis of the clusters obtained by reaction centres. Columns were defined as in bond changes analysis (Table S2). In EC subclasses, the most common subclass is underlined and the number of reactions belonging to each subclass is shown in brackets. Cluster names are arbitrary. Clusters A' to J' obtained by reaction centres do not directly correspond to clusters A to F obtained by bond changes. Number of Most common Outliers and Cluster EC subclasses reactions reaction centres comments EC 5.2 (4), 5.3 (12), EC 5.5.1.19, 5.2.1.5 and carbon atom and A' 38 5.4 (19), 5.5 (2) and 5.3.3.7 are distinct propyl 5.99 (1) reactions. Mixed cluster carbon atom and B' 5 EC 5.2 (5) No outliers. Pure cluster prop-2-en-1-yl carbon atom, 2- C' 56 EC 5.1 (56) hydroxypropyl and 2- No outliers. Pure cluster azanylidenepropyl No outliers. EC 5.1.3.24 is D' 1 EC 5.1 (1) carbon atom a singleton carbon atom, oxygen atom, 2- EC 5.5.1.23, 5.4.2.9 and EC 5.3 (40), 5.4 (9), hydroxypropyl, E' 56 5.5.1.5 are distinct 5.5 (6) and 5.99 (1) hydroxymethyl, reactions. Mixed cluster oxomethylidene and 2-oxopropyl EC 5.5.1.20, 5.5.1.18 and EC 5.2 (1), 5.3 (4), Most of the top 30 F' 46 5.4.99.38 are distinct 5.4 (30) and 5.5 (11) reaction centres reactions. Mixed cluster oxygen atom, EC 5.1.1.11 and 5.3.2.5 are EC 5.1 (1), 5.3 (1) G' 12 hydroxymethyl and distinct reactions. Almost and 5.4 (10) 2-hydroxyethyl pure cluster. carbon atom, oxygen No outliers. EC 5.5.1.3 is a H' 1 EC 5.5 (1) atom and singleton oxomethylidene I' 3 EC 5.4 (3) - No outliers. Pure cluster No outliers. EC 5.2.1.8 is a J' 1 EC 5.2 (1) - singleton

22 Table S4. Analysis of the clusters obtained by substrates and products. Columns were defined as in bond changes and reaction centres analyses (Tables S2 and S3). In EC subclasses, the most common subclass is underlined and the number of reactions belonging to each subclass is shown in brackets. Cluster names are arbitrary. Clusters A'' to E'' obtained by reaction centres do not directly correspond to clusters obtained by bond changes or reaction centres. Number of Cluster EC subclasses Common substrates and products reactions EC 5.1 (9), 5.2 (3), 5.3 (33), 5.4 Geranylgeranyl diphosphate, D-glucose A'' 74 (14) and 5.5 (15) 6-phosphate and prostaglandin H2 EC 5.1 (2), 5.2 (1), 5.3 (6), 5.4 B'' 43 (S)-2,3-epoxysqualene (27), 5.5 (5) and 5.99 (2) C'' 49 EC 5.1 (29), 5.3 (8) and 5.4 (12) dTDP-4-oxo-6-deoxy-D-glucose EC 5.1 (4), 5.2 (7), 5.3 (10) and D'' 28 Methylitaconate and squalene 5.4 (7) E'' 25 EC 5.1 (14) and 5.4 (11) L-glutamate and L-lysine

23 Table S5. List of the 219 isomerase reactions explored in the study. The reaction SMILES column describes the atom-atom mapping of each reaction using a line notation for easy visualisation in chemical editors.

EC Enzyme name Reaction SMILES number [O:3]=[C:2]([OH:4])[CH:1]([NH2:5])[CH3:6]>>[O:3]=[C:2]([OH:4])[CH:1] 5.1.1.1 alanine racemase ([NH2:5])[CH3:6] methionine [O:3]=[C:2]([OH:4])[CH:1]([NH2:9])[CH2:6][CH2:8][S:5][CH3:7]>>[O:3]=[C:2] 5.1.1.2 racemase ([OH:4])[CH:1]([NH2:9])[CH2:6][CH2:8][S:5][CH3:7] [O:8]=[C:7]([OH:10])[CH2:6][CH2:5][CH:1]([NH2:9])[C:2](=[O:3]) 5.1.1.3 glutamate racemase [OH:4]>>[O:8]=[C:7]([OH:10])[CH2:6][CH2:5][CH:1]([NH2:9])[C:2](=[O:3]) [OH:4] [O:3]=[C:2]([OH:4])[CH:1]1[NH:7][CH2:8][CH2:6][CH2:5]1>>[O:3]=[C:2] 5.1.1.4 proline racemase ([OH:4])[CH:1]1[NH:7][CH2:8][CH2:6][CH2:5]1 [O:3]=[C:2]([OH:4])[CH:1]([NH2:10])[CH2:5][CH2:6][CH2:7][CH2:9] 5.1.1.5 lysine racemase [NH2:8]>>[O:3]=[C:2]([OH:4])[CH:1]([NH2:10])[CH2:5][CH2:6][CH2:7][CH2:9] [NH2:8] [O:3]=[C:2]([OH:4])[CH:1]([NH2:8])[CH:5]([OH:6])[CH3:7]>>[O:3]=[C:2] 5.1.1.6 Threonine racemase ([OH:4])[CH:1]([NH2:8])[CH:5]([OH:6])[CH3:7] LL-2,6- [O:3]=[C:2]([OH:4])[CH:1]([NH2:13])[CH2:5][CH2:6][CH2:7][CH:8]([NH2:11]) 5.1.1.7 Diaminoheptanedio [C:9](=[O:10])[OH:12]>>[O:3]=[C:2]([OH:4])[CH:1]([NH2:13])[CH2:5][CH2:6] ate 2-epimerase [CH2:7][CH:8]([NH2:11])[C:9](=[O:10])[OH:12] trans-4-Hydroxy-L- [O:3]=[C:2]([OH:4])[CH:1]1[NH:9][CH2:8][CH:7]([OH:5]) 5.1.1.8 proline 2-epimerase [CH2:6]1>>[O:3]=[C:2]([OH:4])[CH:1]1[NH:9][CH2:8][CH:7]([OH:5])[CH2:6]1 [O:3]=[C:12]([OH:4])[CH:10]([NH2:11])[CH2:9][CH2:8][CH2:7][NH:6][C:1] 5.1.1.9 arginine racemase (=[NH:2])[NH2:5]>>[O:3]=[C:12]([OH:4])[CH:10]([NH2:11])[CH2:9][CH2:8] [CH2:7][NH:6][C:1](=[NH:2])[NH2:5] amino-acid [*:6][CH:1]([NH2:5])[C:2](=[O:3])[OH:4]>>[*:6][CH:1]([NH2:5])[C:2](=[O:3]) 5.1.1.10 racemase [OH:4] [O:21]=[P:20]([OH:24])([OH:30])[O:17][P:9](=[O:10])([OH:14])[O:8][P:31] (=[O:5])([OH:6])[O:29][CH2:28][CH:4]1[O:27][CH:1]([n:12]2[cH:13][n:15] [c:16]3[c:19]([n:23][cH:26][n:25][c:18]32)[NH2:22])[CH:2]([OH:11]) [CH:3]1[OH:7].[O:34]=[C:33]([OH:35])[CH:32]([NH2:43])[CH2:36][c:37]1[cH:38] L-Phenylalanine [cH:39][cH:42][cH:41][cH:40]1.[H:73][OH:44]>>[H:73][O:8][P:31](=[O:5]) 5.1.1.11 racemase (ATP- ([OH:6])[O:29][CH2:28][CH:4]1[O:27][CH:1]([n:12]2[cH:13][n:15][c:16]3[c:19] hydrolysing) ([n:23][cH:26][n:25][c:18]32)[NH2:22])[CH:2]([OH:11])[CH:3]1[OH:7]. [O:34]=[C:33]([OH:35])[CH:32]([NH2:43])[CH2:36][c:37]1[cH:38][cH:39][cH:42] [cH:41][cH:40]1.[O:10]=[P:9]([OH:14])([OH:44])[O:17][P:20](=[O:21])([OH:24]) [OH:30] [O:3]=[C:2]([OH:4])[CH:1]([NH2:9])[CH2:5][CH2:6][CH2:8] 5.1.1.12 ornithine racemase [NH2:7]>>[O:3]=[C:2]([OH:4])[CH:1]([NH2:9])[CH2:5][CH2:6][CH2:8][NH2:7] [O:7]=[C:6]([OH:9])[CH2:5][CH:1]([NH2:8])[C:2](=[O:3])[OH:4]>>[O:7]=[C:6] 5.1.1.13 aspartate racemase ([OH:9])[CH2:5][CH:1]([NH2:8])[C:2](=[O:3])[OH:4] [O:3]=[C:2]([OH:4])[CH:1]([NH2:36])[CH2:5][CH2:7][O:8][c:9]1[cH:10][cH:11] [c:12]([cH:33][cH:32]1)[C:13](=[N:28][OH:31])[C:14](=[O:27])[NH:15] [CH:16]2[C:17](=[O:6])[N:18]([CH2:20]2)[CH:19]([C:21](=[O:22])[OH:23]) Isonocardicin A [c:24]3[cH:25][cH:26][c:29]([OH:30])[cH:35][cH:34]3>>[O:3]=[C:2]([OH:4]) 5.1.1.14 epimerase [CH:1]([NH2:36])[CH2:5][CH2:7][O:8][c:9]1[cH:10][cH:11][c:12]([cH:33] [cH:32]1)[C:13](=[N:28][OH:31])[C:14](=[O:27])[NH:15][CH:16]2[C:17](=[O:6]) [N:18]([CH2:20]2)[CH:19]([C:21](=[O:22])[OH:23])[c:24]3[cH:34][cH:35][c:29] ([OH:30])[cH:26][cH:25]3 5.1.1.15 L-2-Amino-hexano- [O:9]=[C:7]1[NH:6][CH2:1][CH2:2][CH2:3][CH2:4] 6-lactam racemase [CH:5]1[NH2:8]>>[O:9]=[C:7]1[NH:6][CH2:1][CH2:2][CH2:3][CH2:4]

24 [CH:5]1[NH2:8] [*:7][NH:5][C:1](=[O:9])[CH:2]([NH:8][C:10]([*:4])=[O:11])[CH2:3] [Protein]-L-serine 5.1.1.16 [OH:6]>>[*:7][NH:5][C:1](=[O:9])[CH:2]([NH:8][C:10]([*:4])=[O:11])[CH2:3] epimerase [OH:6] [O:3]=[C:2]([OH:4])[CH:1]([NH2:23])[CH2:6][CH2:7][CH2:8][C:9](=[O:22]) [NH:10][CH:11]1[C:12](=[O:19])[N:13]2[CH:21]1[S:24][C:18]([CH3:5]) isopenicillin-N ([CH3:20])[CH:14]2[C:15](=[O:16])[OH:17]>>[O:3]=[C:2]([OH:4])[CH:1] 5.1.1.17 epimerase ([NH2:23])[CH2:6][CH2:7][CH2:8][C:9](=[O:22])[NH:10][CH:11]1[C:12] (=[O:19])[N:13]2[CH:21]1[S:24][C:18]([CH3:5])([CH3:20])[CH:14]2[C:15] (=[O:16])[OH:17] [O:3]=[C:2]([OH:4])[CH:1]([NH2:7])[CH2:6][OH:5]>>[O:3]=[C:2]([OH:4])[CH:1] 5.1.1.18 serine racemase ([NH2:7])[CH2:6][OH:5] (2S)-2-amino-3- [O:8]=[C:11]([NH2:5])[NH:9][O:7][CH2:6][CH:1]([NH2:10])[C:2](=[O:3]) [(carbamoylamino)o 5.1.1.19 [OH:4]>>[O:8]=[C:11]([NH2:5])[NH:9][O:7][CH2:6][CH:1]([NH2:10])[C:2] xy]propanoate 2- (=[O:3])[OH:4] epimerase [O:3]=[C:2]([OH:4])[CH:1]([OH:5])[CH3:6]>>[O:3]=[C:2]([OH:4])[CH:1]([OH:5]) 5.1.2.1 lactate racemase [CH3:6] [O:3]=[C:2]([OH:4])[CH:1]([OH:11])[c:5]1[cH:6][cH:7][cH:10][cH:9] 5.1.2.2 mandelate racemase [cH:8]1>>[O:3]=[C:2]([OH:4])[CH:1]([OH:11])[c:5]1[cH:6][cH:7][cH:10][cH:9] [cH:8]1 [O:3]=[C:2]([S:4][CH2:5][CH2:6][NH:8][C:9](=[O:47])[CH2:11][CH2:12][NH:13] [C:16](=[O:46])[CH:19]([OH:44])[C:22]([CH3:23])([CH3:25])[CH2:26][O:27] [P:28](=[O:29])([OH:32])[O:33][P:34](=[O:36])([OH:37])[O:38][CH2:39] [CH:40]1[O:10][CH:43]([n:14]2[cH:15][n:17][c:18]3[c:21]([n:30][cH:35][n:31] [c:20]32)[NH2:24])[CH:42]([OH:45])[CH:41]1[O:48][P:49](=[O:52])([OH:53]) (S)-3- [OH:7])[CH2:1][CH:50]([OH:54])[CH3:51]>>[O:3]=[C:2]([S:4][CH2:5][CH2:6] 5.1.2.3 Hydroxybutanoyl- [NH:8][C:9](=[O:47])[CH2:11][CH2:12][NH:13][C:16](=[O:46])[CH:19]([OH:44]) CoA 3-epimerase [C:22]([CH3:23])([CH3:25])[CH2:26][O:27][P:28](=[O:29])([OH:32])[O:33][P:34] (=[O:36])([OH:37])[O:38][CH2:39][CH:40]1[O:10][CH:43]([n:14]2[cH:15][n:17] [c:18]3[c:21]([n:30][cH:35][n:31][c:20]32)[NH2:24])[CH:42]([OH:45]) [CH:41]1[O:48][P:49](=[O:52])([OH:53])[OH:7])[CH2:1][CH:50]([OH:54]) [CH3:51] (R)-Acetoin [O:5]=[C:3]([CH3:4])[CH:2]([OH:6])[CH3:1]>>[O:5]=[C:3]([CH3:4])[CH:2] 5.1.2.4 racemase ([OH:6])[CH3:1] (R,R)-Tartrate [O:3]=[C:2]([OH:4])[CH:1]([OH:10])[CH:5]([OH:8])[C:6](=[O:7]) 5.1.2.5 epimerase [OH:9]>>[O:3]=[C:2]([OH:4])[CH:1]([OH:10])[CH:5]([OH:8])[C:6](=[O:7])[OH:9] (1R,2S)-1- [O:13]=[C:11]([OH:5])[CH2:10][CH:6]([C:7](=[O:8])[OH:9])[CH:1]([OH:12])[C:2] Hydroxypropane- 5.1.2.6 (=[O:3])[OH:4]>>[O:13]=[C:11]([OH:5])[CH2:10][CH:6]([C:7](=[O:8])[OH:9]) 1,2,3-tricarboxylate [CH:1]([OH:12])[C:2](=[O:3])[OH:4] 1-epimerase D-Ribulose-5- [O:12]=[C:4]([CH2:5][OH:7])[CH:3]([OH:13])[CH:2]([OH:6])[CH2:1][O:8][P:9] 5.1.3.1 phosphate 3- (=[O:10])([OH:11])[OH:14]>>[O:12]=[C:4]([CH2:5][OH:7])[CH:3]([OH:13]) epimerase [CH:2]([OH:6])[CH2:1][O:8][P:9](=[O:10])([OH:11])[OH:14] [O:8]=[c:3]1[cH:2][cH:1][n:9]([c:10](=[O:11])[nH:4]1)[CH:12]2[O:22][CH:18] ([CH2:23][O:24][P:25](=[O:26])([OH:28])[O:31][P:33](=[O:34])([OH:35])[O:5] [CH:6]3[O:29][CH:30]([CH2:32][OH:36])[CH:15]([OH:17])[CH:13]([OH:19]) UDP-glucose 4- [CH:7]3[OH:27])[CH:16]([OH:20])[CH:14]2[OH:21]>>[O:8]=[c:3]1[cH:2][cH:1] 5.1.3.2 epimerase [n:9]([c:10](=[O:11])[nH:4]1)[CH:12]2[O:22][CH:18]([CH2:23][O:24][P:25] (=[O:26])([OH:28])[O:31][P:33](=[O:34])([OH:35])[O:5][CH:6]3[O:29][CH:30] ([CH2:32][OH:36])[CH:15]([OH:17])[CH:13]([OH:19])[CH:7]3[OH:27])[CH:16] ([OH:20])[CH:14]2[OH:21] [OH:8][CH2:6][CH:5]1[O:10][CH:4]([OH:7])[CH:3]([OH:9])[CH:2]([OH:12]) D-glucose 1- 5.1.3.3 [CH:1]1[OH:11]>>[OH:8][CH2:6][CH:5]1[O:10][CH:4]([OH:7])[CH:3]([OH:9]) epimerase [CH:2]([OH:12])[CH:1]1[OH:11] 5.1.3.4 L-ribulose-5- [O:12]=[C:4]([CH2:5][OH:7])[CH:3]([OH:13])[CH:2]([OH:6])[CH2:1][O:8][P:9]

25 phosphate 4- (=[O:10])([OH:11])[OH:14]>>[O:12]=[C:4]([CH2:5][OH:7])[CH:3]([OH:13]) epimerase [CH:2]([OH:6])[CH2:1][O:8][P:9](=[O:10])([OH:11])[OH:14] [O:7]=[c:3]1[cH:2][cH:1][n:8]([c:9](=[O:10])[nH:4]1)[CH:11]2[O:22][CH:18] ([CH2:23][O:25][P:26](=[O:27])([OH:28])[O:30][P:33](=[O:34])([OH:5])[O:6] [CH:12]3[O:31][CH2:32][CH:17]([OH:19])[CH:15]([OH:24])[CH:14]3[OH:29]) UDP-L-arabinose 4- 5.1.3.5 [CH:16]([OH:20])[CH:13]2[OH:21]>>[O:7]=[c:3]1[cH:2][cH:1][n:8]([c:9] epimerase (=[O:10])[nH:4]1)[CH:11]2[O:22][CH:18]([CH2:23][O:25][P:26](=[O:27]) ([OH:28])[O:30][P:33](=[O:34])([OH:5])[O:6][CH:12]3[O:31][CH2:32][CH:17] ([OH:19])[CH:15]([OH:24])[CH:14]3[OH:29])[CH:16]([OH:20])[CH:13]2[OH:21] [O:32]=[C:30]([OH:33])[CH:29]1[O:28][CH:5]([O:37][P:34](=[O:35])([OH:36]) [O:31][P:25](=[O:26])([OH:27])[O:24][CH2:22][CH:17]2[O:21][CH:12] ([n:9]3[cH:1][cH:2][c:3](=[O:8])[nH:4][c:10]3=[O:11])[CH:14]([OH:20]) UDP-glucuronate 4- [CH:16]2[OH:19])[CH:6]([OH:23])[CH:7]([OH:18]) 5.1.3.6 epimerase [CH:13]1[OH:15]>>[O:32]=[C:30]([OH:33])[CH:29]1[O:28][CH:5]([O:37][P:34] (=[O:35])([OH:36])[O:31][P:25](=[O:26])([OH:27])[O:24][CH2:22][CH:17]2[O:21] [CH:12]([n:9]3[cH:1][cH:2][c:3](=[O:8])[nH:4][c:10]3=[O:11])[CH:14]([OH:20]) [CH:16]2[OH:19])[CH:6]([OH:23])[CH:7]([OH:18])[CH:13]1[OH:15] [O:7]=[c:3]1[cH:2][cH:1][n:8]([c:9](=[O:10])[nH:4]1)[CH:11]2[O:21][CH:16] ([CH2:22][O:24][P:25](=[O:26])([OH:27])[O:29][P:30](=[O:31])([OH:34])[O:36] [CH:37]3[O:32][CH:33]([CH2:35][OH:38])[CH:6]([OH:12])[CH:5]([OH:15]) UDP-N-acetyl-D- [CH:39]3[NH:17][C:20](=[O:28])[CH3:23])[CH:14]([OH:18]) 5.1.3.7 glucosamine 4- [CH:13]2[OH:19]>>[O:7]=[c:3]1[cH:2][cH:1][n:8]([c:9](=[O:10])[nH:4]1) epimerase [CH:11]2[O:21][CH:16]([CH2:22][O:24][P:25](=[O:26])([OH:27])[O:29][P:30] (=[O:31])([OH:34])[O:36][CH:37]3[O:32][CH:33]([CH2:35][OH:38])[CH:6] ([OH:12])[CH:5]([OH:15])[CH:39]3[NH:17][C:20](=[O:28])[CH3:23])[CH:14] ([OH:18])[CH:13]2[OH:19] N-Acyl-D- [*:12][C:9](=[O:11])[NH:8][CH:3]1[CH:4]([OH:7])[O:13][CH:5]([CH2:6][OH:10]) 5.1.3.8 glucosamine 2- [CH:1]([OH:14])[CH:2]1[OH:15]>>[*:12][C:9](=[O:11])[NH:8][CH:3]1[CH:4] epimerase ([OH:7])[O:13][CH:5]([CH2:6][OH:10])[CH:1]([OH:14])[CH:2]1[OH:15] N-Acyl-D- [*:13][C:11](=[O:12])[NH:8][CH:3]1[CH:4]([OH:7])[O:17][CH:16]([CH2:18][O:5] glucosamine 6- [P:6](=[O:9])([OH:10])[OH:14])[CH:1]([OH:19])[CH:2]1[OH:15]>>[*:13][C:11] 5.1.3.9 phosphate 2- (=[O:12])[NH:8][CH:3]1[CH:4]([OH:7])[O:17][CH:16]([CH2:18][O:5][P:6] epimerase (=[O:9])([OH:10])[OH:14])[CH:1]([OH:19])[CH:2]1[OH:15] [O:11]=[c:10]1[n:8][c:3]([NH2:4])[cH:2][cH:1][n:9]1[CH:13]2[O:23][CH:19] ([CH2:24][O:25][P:26](=[O:27])([OH:30])[O:33][P:34](=[O:5])([OH:6])[O:7] CDP-3,6-dideoxy- [CH:12]3[O:29][CH:31]([CH3:32])[CH:17]([OH:20])[CH2:15][CH:14]3[OH:28]) 5.1.3.10 D-glucose 2- [CH:18]([OH:21])[CH:16]2[OH:22]>>[O:11]=[c:10]1[n:8][c:3]([NH2:4])[cH:2] epimerase [cH:1][n:9]1[CH:13]2[O:23][CH:19]([CH2:24][O:25][P:26](=[O:27])([OH:30]) [O:33][P:34](=[O:5])([OH:6])[O:7][CH:12]3[O:29][CH:31]([CH3:32])[CH:17] ([OH:20])[CH2:15][CH:14]3[OH:28])[CH:18]([OH:21])[CH:16]2[OH:22] [OH:9][CH2:5][CH:4]1[O:17][CH:15]([O:18][CH:19]2[CH:21]([OH:10])[CH:23] ([OH:8])[CH:6]([OH:7])[O:20][CH:13]2[CH2:14][OH:16])[CH:1]([OH:22])[CH:2] Cellobiose 2- 5.1.3.11 ([OH:12])[CH:3]1[OH:11]>>[OH:9][CH2:5][CH:4]1[O:17][CH:15]([O:18] epimerase [CH:19]2[CH:21]([OH:10])[CH:23]([OH:8])[CH:6]([OH:7])[O:20] [CH:13]2[CH2:14][OH:16])[CH:1]([OH:22])[CH:2]([OH:12])[CH:3]1[OH:11] [O:32]=[C:30]([OH:33])[CH:29]1[O:28][CH:5]([O:37][P:34](=[O:35])([OH:36]) [O:31][P:25](=[O:26])([OH:27])[O:24][CH2:22][CH:17]2[O:21][CH:12] ([n:9]3[cH:1][cH:2][c:3](=[O:8])[nH:4][c:10]3=[O:11])[CH:14]([OH:20]) UDP-glucuronate [CH:16]2[OH:19])[CH:6]([OH:23])[CH:7]([OH:18]) 5.1.3.12 5'-epimerase [CH:13]1[OH:15]>>[O:32]=[C:30]([OH:33])[CH:29]1[O:28][CH:5]([O:37][P:34] (=[O:35])([OH:36])[O:31][P:25](=[O:26])([OH:27])[O:24][CH2:22][CH:17]2[O:21] [CH:12]([n:9]3[cH:1][cH:2][c:3](=[O:8])[nH:4][c:10]3=[O:11])[CH:14]([OH:20]) [CH:16]2[OH:19])[CH:6]([OH:23])[CH:7]([OH:18])[CH:13]1[OH:15] 5.1.3.13 dTDP-4-dehydro-6- [O:6]=[c:3]1[nH:4][c:12](=[O:14])[n:11]([cH:1][c:2]1[CH3:10])[CH:18]2[O:25] deoxy-alpha-D- [CH:22]([CH2:26][O:27][P:28](=[O:29])([OH:31])[O:34][P:35](=[O:5])([OH:7]) glucose 3,5- [O:8][CH:9]3[O:30][CH:32]([C:16](=[O:17])[CH:15]([OH:20])[CH:13]3[OH:24]) epimerase [CH3:33])[CH:21]([OH:23])[CH2:19]2>>[O:6]=[c:3]1[nH:4][c:12](=[O:14])[n:11] ([cH:1][c:2]1[CH3:10])[CH:18]2[O:25][CH:22]([CH2:26][O:27][P:28](=[O:29])

26 ([OH:31])[O:34][P:35](=[O:5])([OH:7])[O:8][CH:9]3[O:30][CH:32]([C:16] (=[O:17])[CH:15]([OH:20])[CH:13]3[OH:24])[CH3:33])[CH:21]([OH:23]) [CH2:19]2 [O:7]=[c:3]1[cH:2][cH:1][n:8]([c:9](=[O:10])[nH:4]1)[CH:11]2[O:21][CH:16] ([CH2:22][O:24][P:25](=[O:26])([OH:27])[O:29][P:30](=[O:31])([OH:34])[O:36] [CH:37]3[O:32][CH:33]([CH2:35][OH:38])[CH:6]([OH:12])[CH:5]([OH:15]) UDP-N-acetyl-D- [CH:39]3[NH:17][C:20](=[O:28])[CH3:23])[CH:14]([OH:18]) 5.1.3.14 glucosamine 2- [CH:13]2[OH:19]>>[O:7]=[c:3]1[cH:2][cH:1][n:8]([c:9](=[O:10])[nH:4]1) epimerase [CH:11]2[O:21][CH:16]([CH2:22][O:24][P:25](=[O:26])([OH:27])[O:29][P:30] (=[O:31])([OH:34])[O:36][CH:37]3[O:32][CH:33]([CH2:35][OH:38])[CH:6] ([OH:12])[CH:5]([OH:15])[CH:39]3[NH:17][C:20](=[O:28])[CH3:23])[CH:14] ([OH:18])[CH:13]2[OH:19] [O:8]=[P:6]([OH:9])([OH:11])[O:5][CH2:15][CH:13]1[O:14][CH:4]([OH:7])[CH:3] alpha-D-Glucose 6- ([OH:10])[CH:2]([OH:12])[CH:1]1[OH:16]>>[O:8]=[P:6]([OH:9])([OH:11])[O:5] 5.1.3.15 phosphate ketol- [CH2:15][CH:13]1[O:14][CH:4]([OH:7])[CH:3]([OH:10])[CH:2]([OH:12]) isomerase [CH:1]1[OH:16] [O:8]=[c:3]1[cH:2][cH:1][n:9]([c:10](=[O:11])[nH:4]1)[CH:12]2[O:22][CH:18] ([CH2:23][O:24][P:25](=[O:26])([OH:28])[O:30][P:33](=[O:34])([OH:35])[O:5] [CH:6]3[O:29][CH:31]([CH2:32][OH:36])[CH:15]([OH:17])[CH:13]([OH:19]) UDP-glucosamine [CH:7]3[NH2:27])[CH:16]([OH:20])[CH:14]2[OH:21]>>[O:8]=[c:3]1[cH:2][cH:1] 5.1.3.16 4-epimerase [n:9]([c:10](=[O:11])[nH:4]1)[CH:12]2[O:22][CH:18]([CH2:23][O:24][P:25] (=[O:26])([OH:28])[O:30][P:33](=[O:34])([OH:35])[O:5][CH:6]3[O:29][CH:31] ([CH2:32][OH:36])[CH:15]([OH:17])[CH:13]([OH:19])[CH:7]3[NH2:27])[CH:16] ([OH:20])[CH:14]2[OH:21] [*:14][O:12][CH:11]1[O:13][CH:27]([CH2:28][OH:6])[CH:8]([O:7][CH:5]2[O:29] Heparosan-N- [CH:22]([C:23](=[O:24])[OH:25])[CH:2]([*:1])[CH:3]([OH:21])[CH:4]2[OH:17]) sulfate D- [CH:9]([OH:26])[CH:10]1[NH:15][S:16](=[O:18])(=[O:19])[OH:20]>>[*:14][O:12] 5.1.3.17 glucuronate [CH:11]1[O:13][CH:27]([CH2:28][OH:6])[CH:8]([O:7][CH:5]2[O:29][CH:22] glucurono-5- ([C:23](=[O:24])[OH:25])[CH:2]([*:1])[CH:3]([OH:21])[CH:4]2[OH:17])[CH:9] epimerase ([OH:26])[CH:10]1[NH:15][S:16](=[O:18])(=[O:19])[OH:20] [O:37]=[c:36]1[nH:34][c:1]([n:2][c:3]2[c:4]1[n:5][cH:6][n:7]2[CH:8]3[O:16] [CH:11]([CH2:17][O:18][P:20](=[O:21])([OH:22])[O:23][P:25](=[O:27])([OH:29]) [O:30][CH:31]4[O:19][CH:24]([CH2:26][OH:28])[CH:38]([OH:39])[CH:35] ([OH:12])[CH:32]4[OH:14])[CH:10]([OH:13])[CH:9]3[OH:15]) GDP-mannose 3,5- 5.1.3.18 [NH2:33]>>[O:37]=[c:36]1[nH:34][c:1]([n:2][c:3]2[c:4]1[n:5][cH:6] epimerase [n:7]2[CH:8]3[O:16][CH:11]([CH2:17][O:18][P:20](=[O:21])([OH:22])[O:23] [P:25](=[O:27])([OH:29])[O:30][CH:31]4[O:19][CH:24]([CH2:26][OH:28]) [CH:38]([OH:39])[CH:35]([OH:12])[CH:32]4[OH:14])[CH:10]([OH:13]) [CH:9]3[OH:15])[NH2:33] [*:25][O:24][CH:21]1[O:14][CH:10]([CH2:11][OH:13])[CH:9]([OH:16])[CH:8] ([O:7][CH:5]2[O:27][CH:19]([C:20](=[O:22])[OH:23])[CH:2]([*:1])[CH:3] Chondroitin-D- ([OH:17])[CH:4]2[OH:15])[CH:18]1[NH:26][C:28](=[O:12])[CH3:6]>>[*:25] 5.1.3.19 glucuronate 5- [O:24][CH:21]1[O:14][CH:10]([CH2:11][OH:13])[CH:9]([OH:16])[CH:8]([O:7] epimerase [CH:5]2[O:27][CH:19]([C:20](=[O:22])[OH:23])[CH:2]([*:1])[CH:3]([OH:17]) [CH:4]2[OH:15])[CH:18]1[NH:26][C:28](=[O:12])[CH3:6] [O:30]=[P:29]([OH:32])([O:33][CH2:34][CH:35]1[O:9][CH:39]([n:11]2[cH:12] [n:15][c:17]3[c:25]([n:28][cH:36][n:31][c:23]32)[NH2:26])[CH:38]([OH:7]) [CH:37]1[OH:8])[O:27][P:21](=[O:22])([OH:24])[O:20][CH:18]4[O:19][CH:4] ADP-D-glycero-D- ([CH:5]([OH:13])[CH2:6][OH:10])[CH:3]([OH:14])[CH:2]([OH:16]) 5.1.3.20 manno-heptose 6- [CH:1]4[OH:40]>>[O:30]=[P:29]([OH:32])([O:33][CH2:34][CH:35]1[O:9][CH:39] epimerase ([n:11]2[cH:12][n:15][c:17]3[c:25]([n:28][cH:36][n:31][c:23]32)[NH2:26])[CH:38] ([OH:7])[CH:37]1[OH:8])[O:27][P:21](=[O:22])([OH:24])[O:20][CH:18]4[O:19] [CH:4]([CH:5]([OH:13])[CH2:6][OH:10])[CH:3]([OH:14])[CH:2]([OH:16]) [CH:1]4[OH:40] [OH:9][CH2:5][CH:4]1[O:17][CH:15]([O:18][CH:19]2[CH:21]([OH:10])[CH:23] ([OH:8])[CH:6]([OH:7])[O:20][CH:13]2[CH2:14][OH:16])[CH:1]([OH:22])[CH:2] maltose 1- 5.1.3.21 ([OH:12])[CH:3]1[OH:11]>>[OH:9][CH2:5][CH:4]1[O:17][CH:15]([O:18] epimerase [CH:19]2[CH:21]([OH:10])[CH:23]([OH:8])[CH:6]([OH:7])[O:20] [CH:13]2[CH2:14][OH:16])[CH:1]([OH:22])[CH:2]([OH:12])[CH:3]1[OH:11]

27 L-ribulose-5- [O:12]=[C:4]([CH2:5][OH:7])[CH:3]([OH:13])[CH:2]([OH:6])[CH2:1][O:8][P:9] 5.1.3.22 phosphate 3- (=[O:10])([OH:11])[OH:14]>>[O:12]=[C:4]([CH2:5][OH:7])[CH:3]([OH:13]) epimerase; [CH:2]([OH:6])[CH2:1][O:8][P:9](=[O:10])([OH:11])[OH:14] [O:38]=[C:36]([OH:39])[CH:35]1[O:34][CH:37]([O:33][P:29](=[O:31])([OH:32]) [O:28][P:23](=[O:24])([OH:26])[O:22][CH2:20][CH:15]2[O:19][CH:10] ([n:7]3[cH:1][cH:2][c:3](=[O:6])[nH:4][c:8]3=[O:9])[CH:12]([OH:18]) 2,3-diacetamido- [CH:14]2[OH:17])[CH:40]([NH:21][C:25](=[O:30])[CH3:27])[CH:41]([NH:5] 2,3-dideoxy-alpha- 5.1.3.23 [C:11](=[O:16])[CH3:13])[CH:42]1[OH:43]>>[O:38]=[C:36]([OH:39]) D-glucuronate 2- [CH:35]1[O:34][CH:37]([O:33][P:29](=[O:31])([OH:32])[O:28][P:23](=[O:24]) epimerase ([OH:26])[O:22][CH2:20][CH:15]2[O:19][CH:10]([n:7]3[cH:1][cH:2][c:3](=[O:6]) [nH:4][c:8]3=[O:9])[CH:12]([OH:18])[CH:14]2[OH:17])[CH:40]([NH:21][C:25] (=[O:30])[CH3:27])[CH:41]([NH:5][C:11](=[O:16])[CH3:13])[CH:42]1[OH:43] [O:3]=[C:2]([OH:4])[C:1]1([OH:7])[O:10][CH:11]([CH:13]([OH:21])[CH:14] N-acetyl-alpha- ([OH:20])[CH2:16][OH:17])[CH:8]([NH:9][C:12](=[O:18])[CH3:15])[CH:6] 5.1.3.24 neuraminate 2- ([OH:19])[CH2:5]1>>[O:3]=[C:2]([OH:4])[C:1]1([OH:7])[O:10][CH:11]([CH:13] epimerase ([OH:21])[CH:14]([OH:20])[CH2:16][OH:17])[CH:8]([NH:9][C:12](=[O:18]) [CH3:15])[CH:6]([OH:19])[CH2:5]1 [O:6]=[c:3]1[nH:4][c:12](=[O:14])[n:11]([cH:1][c:2]1[CH3:10])[CH:18]2[O:24] [CH:21]([CH2:25][O:26][P:27](=[O:29])([OH:31])[O:34][P:35](=[O:5])([OH:7]) [O:8][CH:9]3[O:30][CH:32]([CH3:33])[CH:16]([OH:17])[CH:15]([OH:23]) dTDP-6-deoxy- [CH:13]3[OH:28])[CH:20]([OH:22])[CH2:19]2>>[O:6]=[c:3]1[nH:4][c:12] 5.1.3.25 beta-L-talose 4- (=[O:14])[n:11]([cH:1][c:2]1[CH3:10])[CH:18]2[O:24][CH:21]([CH2:25][O:26] epimerase [P:27](=[O:29])([OH:31])[O:34][P:35](=[O:5])([OH:7])[O:8][CH:9]3[O:30][CH:32] ([CH3:33])[CH:16]([OH:17])[CH:15]([OH:23])[CH:13]3[OH:28])[CH:20] ([OH:22])[CH2:19]2 [O:72]=[C:66]([NH:64][CH:56]1[CH:55]([O:76][CH:78]([CH2:44][OH:50]) [CH:59]([OH:60])[CH:58]1[OH:61])[O:54][P:51](=[O:52])([OH:53])[O:49][P:46] (=[O:47])([OH:48])[O:45][CH2:43][CH:42]=[C:41]([CH3:57])[CH2:40][CH2:39] [CH:38]=[C:37]([CH3:62])[CH2:36][CH2:35][CH:34]=[C:33]([CH3:63])[CH2:32] [CH2:31][CH:30]=[C:29]([CH3:65])[CH2:28][CH2:27][CH:26]=[C:25]([CH3:68]) [CH2:24][CH2:23][CH:22]=[C:21]([CH3:69])[CH2:20][CH2:19][CH:18]=[C:17] N-acetyl-alpha-D- ([CH3:70])[CH2:16][CH2:15][CH:14]=[C:13]([CH3:71])[CH2:12][CH2:11] glucosaminyl- [CH:10]=[C:9]([CH3:73])[CH2:8][CH2:7][CH:6]=[C:5]([CH3:74])[CH2:4][CH2:3] diphospho- [CH:2]=[C:1]([CH3:75])[CH3:77])[CH3:67]>>[O:72]=[C:66]([NH:64] 5.1.3.26 ditrans,octacis- [CH:56]1[CH:55]([O:76][CH:78]([CH2:44][OH:50])[CH:59]([OH:60]) undecaprenol 4- [CH:58]1[OH:61])[O:54][P:51](=[O:52])([OH:53])[O:49][P:46](=[O:47])([OH:48]) epimerase [O:45][CH2:43][CH:42]=[C:41]([CH3:57])[CH2:40][CH2:39][CH:38]=[C:37] ([CH3:62])[CH2:36][CH2:35][CH:34]=[C:33]([CH3:63])[CH2:32][CH2:31] [CH:30]=[C:29]([CH3:65])[CH2:28][CH2:27][CH:26]=[C:25]([CH3:68])[CH2:24] [CH2:23][CH:22]=[C:21]([CH3:69])[CH2:20][CH2:19][CH:18]=[C:17]([CH3:70]) [CH2:16][CH2:15][CH:14]=[C:13]([CH3:71])[CH2:12][CH2:11][CH:10]=[C:9] ([CH3:73])[CH2:8][CH2:7][CH:6]=[C:5]([CH3:74])[CH2:4][CH2:3][CH:2]=[C:1] ([CH3:75])[CH3:77])[CH3:67] [O:6]=[c:3]1[nH:4][c:12](=[O:14])[n:11]([cH:1][c:2]1[CH3:10])[CH:18]2[O:25] [CH:22]([CH2:26][O:27][P:28](=[O:29])([OH:31])[O:34][P:35](=[O:5])([OH:7]) [O:8][CH:9]3[O:30][CH:32]([C:16](=[O:17])[CH:15]([OH:20])[CH:13]3[OH:24]) dTDP-4-dehydro-6- [CH3:33])[CH:21]([OH:23])[CH2:19]2>>[O:6]=[c:3]1[nH:4][c:12](=[O:14])[n:11] 5.1.3.27 deoxy-alpha-D- ([cH:1][c:2]1[CH3:10])[CH:18]2[O:25][CH:22]([CH2:26][O:27][P:28](=[O:29]) glucose 3-epimerase ([OH:31])[O:34][P:35](=[O:5])([OH:7])[O:8][CH:9]3[O:30][CH:32]([C:16] (=[O:17])[CH:15]([OH:20])[CH:13]3[OH:24])[CH3:33])[CH:21]([OH:23]) [CH2:19]2 5.1.99.1 Methylmalonyl- [O:3]=[C:2]([OH:4])[CH:1]([C:6](=[O:7])[S:8][CH2:9][CH2:11][NH:12][C:14] CoA epimerase (=[O:52])[CH2:15][CH2:16][NH:18][C:21](=[O:51])[CH:24]([OH:50])[C:25] ([CH3:28])([CH3:26])[CH2:30][O:31][P:33](=[O:34])([OH:35])[O:36][P:38] (=[O:41])([OH:42])[O:43][CH2:44][CH:45]1[O:17][CH:48]([n:19]2[cH:20][n:22] [c:23]3[c:29]([n:37][cH:40][n:39][c:27]32)[NH2:32])[CH:47]([OH:49]) [CH:46]1[O:53][P:55](=[O:5])([OH:10])[OH:13])[CH3:54]>>[O:3]=[C:2]([OH:4]) [CH:1]([C:6](=[O:7])[S:8][CH2:9][CH2:11][NH:12][C:14](=[O:52])[CH2:15] [CH2:16][NH:18][C:21](=[O:51])[CH:24]([OH:50])[C:25]([CH3:26])([CH3:28])

28 [CH2:30][O:31][P:33](=[O:34])([OH:35])[O:36][P:38](=[O:41])([OH:42])[O:43] [CH2:44][CH:45]1[O:17][CH:48]([n:19]2[cH:20][n:22][c:23]3[c:29]([n:37][cH:40] [n:39][c:27]32)[NH2:32])[CH:47]([OH:49])[CH:46]1[O:53][P:55](=[O:5]) ([OH:10])[OH:13])[CH3:54] [OH:11][CH:6]1[CH2:10][CH2:9][C:7]2([CH3:8])[CH:4]([CH2:3][CH2:2] 16alpha- [CH:1]3[CH:17]2[CH2:18][CH2:19][C:20]4([CH3:21])[CH2:15][CH:14]([OH:16]) 5.1.99.2 Hydroxysteroid 16- [CH2:13][CH:12]34)[CH2:5]1>>[OH:11][CH:6]1[CH2:10][CH2:9][C:7]2([CH3:8]) epimerase [CH:4]([CH2:3][CH2:2][CH:1]3[CH:17]2[CH2:18][CH2:19][C:20]4([CH3:21]) [CH2:15][CH:14]([OH:16])[CH2:13][CH:12]34)[CH2:5]1 [O:9]=[C:5]([NH2:7])[NH:4][CH:2]1[NH:11][C:3](=[O:8])[NH:6] (S)(+)-allantoin 5.1.99.3 [C:1]1=[O:10]>>[O:9]=[C:5]([NH2:7])[NH:4][CH:2]1[NH:11][C:3](=[O:8])[NH:6] racemase [C:1]1=[O:10] [*:52][CH:1]([C:2](=[O:3])[S:4][CH2:5][CH2:6][NH:8][C:9](=[O:48])[CH2:10] [CH2:11][NH:12][C:15](=[O:46])[CH:18]([OH:44])[C:21]([CH3:22])([CH3:24]) [CH2:26][O:27][P:28](=[O:29])([OH:31])[O:32][P:33](=[O:35])([OH:37])[O:38] [CH2:39][CH:40]1[O:13][CH:43]([n:14]2[cH:16][n:17][c:19]3[c:23]([n:30][cH:36] [n:34][c:20]32)[NH2:25])[CH:42]([OH:45])[CH:41]1[O:47][P:49](=[O:51]) (2S)-2-Methylacyl- 5.1.99.4 ([OH:53])[OH:7])[CH3:50]>>[*:52][CH:1]([C:2](=[O:3])[S:4][CH2:5][CH2:6] CoA 2-epimerase [NH:8][C:9](=[O:48])[CH2:10][CH2:11][NH:12][C:15](=[O:46])[CH:18]([OH:44]) [C:21]([CH3:22])([CH3:24])[CH2:26][O:27][P:28](=[O:29])([OH:31])[O:32][P:33] (=[O:35])([OH:37])[O:38][CH2:39][CH:40]1[O:13][CH:43]([n:14]2[cH:16][n:17] [c:19]3[c:23]([n:30][cH:36][n:34][c:20]32)[NH2:25])[CH:42]([OH:45]) [CH:41]1[O:47][P:49](=[O:51])([OH:53])[OH:7])[CH3:50] D-5- [*:6][CH:2]1[NH:4][C:5](=[O:3])[NH:8][C:1]1=[O:7]>>[*:6][CH:2]1[NH:4][C:5] 5.1.99.5 monosubstituted- (=[O:3])[NH:8][C:1]1=[O:7] hydantoin racemase [O:7]=[C:3]([NH2:4])[C:2]1=[CH:1][N:15]([CH:16]([OH:18])[CH2:13][CH2:12]1) [CH:21]2[O:28][CH:24]([CH2:29][O:34][P:35](=[O:36])([OH:38])[O:39][P:40] (6R)-6beta- (=[O:41])([OH:44])[O:45][CH2:5][CH:6]3[O:17][CH:10]([n:19]4[cH:20][n:26] hydroxy-1,4,5,6- [c:30]5[c:32]([n:37][cH:43][n:42][c:31]54)[NH2:33])[CH:9]([OH:11]) tetrahydronicotinam [CH:8]3[OH:14])[CH:23]([OH:25])[CH:22]2[OH:27]>>[O:7]=[C:3]([NH2:4]) 5.1.99.6 ide-adenine- [C:2]1=[CH:1][N:15]([CH:16]([OH:18])[CH2:13][CH2:12]1)[CH:21]2[O:28] dinucleotide 6- [CH:24]([CH2:29][O:34][P:35](=[O:36])([OH:38])[O:39][P:40](=[O:41])([OH:44]) epimerase [O:45][CH2:5][CH:6]3[O:17][CH:10]([n:19]4[cH:20][n:26][c:30]5[c:32]([n:37] [cH:43][n:42][c:31]54)[NH2:33])[CH:9]([OH:11])[CH:8]3[OH:14])[CH:23] ([OH:25])[CH:22]2[OH:27] Maleate cis-trans- [O:4]=[C:3]([OH:5])[CH:2]=[CH:1][C:8](=[O:6])[OH:7]>>[O:4]=[C:3]([OH:5]) 5.2.1.1 isomerase [CH:2]=[CH:1][C:8](=[O:6])[OH:7] 4- [O:4]=[C:3]([OH:5])[CH:2]=[CH:1][C:6](=[O:13])[CH2:7][C:8](=[O:11])[CH2:9] 5.2.1.2 Maleylacetoacetate [C:10](=[O:12])[OH:14]>>[O:4]=[C:3]([OH:5])[CH:2]=[CH:1][C:6](=[O:13]) cis-trans-isomerase [CH2:7][C:8](=[O:11])[CH2:9][C:10](=[O:12])[OH:14] [O:4]=[C:3]([OH:5])[CH:2]=[CH:1][C:7](=[O:12])[CH2:8][C:9](=[O:6])[C:10] 3-Maleylpyruvate 5.2.1.4 (=[O:11])[OH:13]>>[O:4]=[C:3]([OH:5])[CH:2]=[CH:1][C:7](=[O:12])[CH2:8] cis-trans-isomerase [C:9](=[O:6])[C:10](=[O:11])[OH:13] [H:34][CH:3]([CH:2]=[CH:1][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]) 9-cis,12-cis- [CH:4]=[CH:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13] Octadecadienoate 5.2.1.5 (=[O:14])[OH:15]>>[H:34][CH:1]([CH:2]=[CH:3][CH:4]=[CH:5][CH2:6][CH2:7] delta12-cis-delta11- [CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13](=[O:14])[OH:15])[CH2:16] trans-isomerase [CH2:17][CH2:18][CH2:19][CH3:20] (E)-2-(2-Furyl)-3- [O:18]=[C:15]([NH2:16])[C:1](=[CH:2][c:3]1[o:9][c:6]([cH:5][cH:4]1)[N+:10] (5-nitro-2- (=[O:13])[O-:12])[c:7]2[o:17][cH:14][cH:11][cH:8]2>>[O:18]=[C:15]([NH2:16]) 5.2.1.6 furyl)acrylamide [C:1](=[CH:2][c:3]1[o:9][c:6]([cH:5][cH:4]1)[N+:10](=[O:13])[O-:12])[c:7]2[o:17] cis-trans-isomerase [cH:14][cH:11][cH:8]2 [*:9][NH:8][C:7](=[O:10])[CH:4]1[N:11]([C:12]([*:6])=[O:5])[CH2:1][CH2:2] Peptidylproline cis- 5.2.1.8 [CH2:3]1>>[*:9][NH:8][C:7](=[O:10])[CH:4]1[N:11]([C:12]([*:6])=[O:5])[CH2:1] trans-isomerase [CH2:2][CH2:3]1 5.2.1.9 (2E,6E)-farnesol 2- [OH:14][CH2:11][CH:10]=[C:9]([CH3:12])[CH2:8][CH2:7][CH:6]=[C:5]

29 ([CH3:13])[CH2:4][CH2:3][CH:2]=[C:1]([CH3:15])[CH3:16]>>[OH:14][CH2:11] cis-trans-isomerase [CH:10]=[C:9]([CH3:12])[CH2:8][CH2:7][CH:6]=[C:5]([CH3:13])[CH2:4][CH2:3] [CH:2]=[C:1]([CH3:15])[CH3:16] cis-2-Chloro-4- [O:6]=[C:5]([OH:7])[CH:4]=[C:3]1[O:11][C:8](=[O:9])[C:1] carboxymethyleneb 5.2.1.10 ([Cl:10])=[CH:2]1>>[O:6]=[C:5]([OH:7])[CH:4]=[C:3]1[O:11][C:8](=[O:9])[C:1] ut-2-en-1,4-olide ([Cl:10])=[CH:2]1 cis-trans-isomerase [CH:7](=[CH:8][CH:9]=[C:10]([CH:11]=[CH:12][CH:13]=[C:14]([CH3:15]) [CH2:16][CH2:17][CH:18]=[C:19]([CH3:20])[CH2:23][CH2:27][CH:31]=[C:35] ([CH3:36])[CH3:39])[CH3:21])[CH:6]=[C:5]([CH:4]=[CH:3][CH:2]=[C:1] ([CH3:24])[CH2:25][CH2:26][CH:28]=[C:29]([CH3:30])[CH2:32][CH2:33] 9,15,9'-tricis-zeta- [CH:34]=[C:37]([CH3:38])[CH3:40])[CH3:22]>>[CH:7](=[CH:8][CH:9]=[C:10] 5.2.1.12 carotene cis-trans- ([CH:11]=[CH:12][CH:13]=[C:14]([CH3:15])[CH2:16][CH2:17][CH:18]=[C:19] isomerase ([CH3:20])[CH2:23][CH2:27][CH:31]=[C:35]([CH3:36])[CH3:39])[CH3:21]) [CH:6]=[C:5]([CH:4]=[CH:3][CH:2]=[C:1]([CH3:24])[CH2:25][CH2:26] [CH:28]=[C:29]([CH3:30])[CH2:32][CH2:33][CH:34]=[C:37]([CH3:38])[CH3:40]) [CH3:22] [CH:11](=[CH:12][CH:13]=[C:14]([CH:15]=[CH:16][CH:17]=[C:18] ([CH:19]=[CH:20][CH:21]=[C:22]([CH3:23])[CH2:24][CH2:25][CH:26]=[C:29] ([CH3:31])[CH3:39])[CH3:27])[CH3:28])[CH:10]=[C:9]([CH:8]=[CH:7] [CH:6]=[C:5]([CH:4]=[CH:3][CH:2]=[C:1]([CH3:33])[CH2:34][CH2:35] 7,9,7',9'-tetracis- [CH:36]=[C:37]([CH3:38])[CH3:40])[CH3:32])[CH3:30]>>[CH:11](=[CH:12] 5.2.1.13 lycopene cis-trans- [CH:13]=[C:14]([CH:15]=[CH:16][CH:17]=[C:18]([CH:19]=[CH:20] isomerase [CH:21]=[C:22]([CH3:23])[CH2:24][CH2:25][CH:26]=[C:29]([CH3:31])[CH3:39]) [CH3:27])[CH3:28])[CH:10]=[C:9]([CH:8]=[CH:7][CH:6]=[C:5]([CH:4]=[CH:3] [CH:2]=[C:1]([CH3:33])[CH2:34][CH2:35][CH:36]=[C:37]([CH3:38])[CH3:40]) [CH3:32])[CH3:30] [CH:11](=[CH:12][CH:13]=[C:14]([CH:15]=[CH:16][CH:17]=[C:18] ([CH:19]=[CH:20][C:21]1=[C:22]([CH3:23])[CH2:26][CH2:27][CH2:24] [C:33]1([CH3:35])[CH3:38])[CH3:25])[CH3:28])[CH:10]=[C:9]([CH:8]=[CH:7] [CH:6]=[C:5]([CH:4]=[CH:3][C:2]2=[C:1]([CH3:37])[CH2:39][CH2:40][CH2:36] beta-carotene 9-cis- [C:31]2([CH3:32])[CH3:34])[CH3:30])[CH3:29]>>[CH:11](=[CH:12] 5.2.1.14 all-trans isomerase [CH:13]=[C:14]([CH:15]=[CH:16][CH:17]=[C:18]([CH:19]=[CH:20] [C:21]1=[C:22]([CH3:23])[CH2:26][CH2:27][CH2:24][C:33]1([CH3:35])[CH3:38]) [CH3:25])[CH3:28])[CH:10]=[C:9]([CH:8]=[CH:7][CH:6]=[C:5]([CH:4]=[CH:3] [C:2]2=[C:1]([CH3:37])[CH2:39][CH2:40][CH2:36][C:31]2([CH3:32])[CH3:34]) [CH3:30])[CH3:29] D-glyceraldehyde- [H:14][O:9][C:2]([H:13])([CH:3]=[O:6])[CH2:1][O:4][P:5](=[O:7])([OH:8]) 5.3.1.1 3-phosphate aldose- [OH:10]>>[H:14][O:6][CH:3]([H:13])[C:2](=[O:9])[CH2:1][O:4][P:5](=[O:7]) ketose-isomerase ([OH:8])[OH:10] [H:12][C:4]1([OH:6])[CH:8]([OH:10])[O:7][CH2:1][CH:2]([OH:5]) D-arabinose aldose- 5.3.1.3 [CH:3]1[OH:9]>>[H:12][CH:8]([OH:10])[C:4]1([OH:6])[O:7][CH2:1][CH:2] ketose-isomerase ([OH:5])[CH:3]1[OH:9] [H:12][C:4]1([OH:6])[CH:8]([OH:10])[O:7][CH2:1][CH:2]([OH:5]) L-Arabinose aldose- 5.3.1.4 [CH:3]1[OH:9]>>[H:12][CH:8]([OH:10])[C:4]1([OH:6])[O:7][CH2:1][CH:2] ketose-isomerase ([OH:5])[CH:3]1[OH:9] [H:12][C:4]1([OH:6])[CH:8]([OH:10])[O:7][CH2:1][CH:2]([OH:5]) D-xylose aldose- 5.3.1.5 [CH:3]1[OH:9]>>[H:12][CH:8]([OH:10])[C:4]1([OH:6])[O:7][CH2:1][CH:2] ketose-isomerase ([OH:5])[CH:3]1[OH:9] [H:21][O:10][C:2]1([H:19])[CH:1]([OH:12])[O:14][CH:4]([CH2:5][O:7][P:8] D-ribose-5- (=[O:9])([OH:11])[OH:13])[CH:3]1[OH:6]>>[H:21][O:14][CH:4]([CH2:5][O:7] 5.3.1.6 phosphate aldose- [P:8](=[O:9])([OH:11])[OH:13])[CH:3]([OH:6])[C:2](=[O:10])[CH:1]([H:19]) ketose-isomerase [OH:12] [H:18][C:3]1([OH:9])[CH:4]([OH:7])[O:10][CH:5]([CH2:6][OH:8])[CH:1] D-mannose aldose- 5.3.1.7 ([OH:11])[CH:2]1[OH:12]>>[H:18][CH:4]([OH:7])[C:3]1([OH:9])[O:10][CH:5] ketose-isomerase ([CH2:6][OH:8])[CH:1]([OH:11])[CH:2]1[OH:12] 5.3.1.8 D-mannose-6- [H:21][C:3]1([OH:10])[CH:4]([OH:7])[O:14][CH:13]([CH2:15][O:5][P:6](=[O:8])

30 ([OH:9])[OH:11])[CH:1]([OH:16])[CH:2]1[OH:12]>>[H:21][CH:4]([OH:7]) phosphate aldose- [C:3]1([OH:10])[O:14][CH:13]([CH2:15][O:5][P:6](=[O:8])([OH:11])[OH:9]) ketose-isomerase [CH:1]([OH:16])[CH:2]1[OH:12] [H:21][C:3]1([OH:10])[CH:4]([OH:7])[O:14][CH:13]([CH2:15][O:5][P:6](=[O:8]) D-glucose-6- ([OH:9])[OH:11])[CH:1]([OH:16])[CH:2]1[OH:12]>>[H:21][CH:4]([OH:7]) 5.3.1.9 phosphate aldose- [C:3]1([OH:10])[O:14][CH:13]([CH2:15][O:5][P:6](=[O:8])([OH:11])[OH:9]) ketose-isomerase [CH:1]([OH:16])[CH:2]1[OH:12] D-glucuronate [H:18][C:7]1([OH:10])[CH:11]([OH:12])[O:9][CH:1]([C:2](=[O:3])[OH:4])[CH:5] 5.3.1.12 aldose-ketose- ([OH:8])[CH:6]1[OH:13]>>[H:18][CH:11]([OH:12])[C:7]1([OH:10])[O:9][CH:1] isomerase ([C:2](=[O:3])[OH:4])[CH:5]([OH:8])[CH:6]1[OH:13] D-arabinose-5- [H:21][O:10][C:4]([H:19])([CH:5]=[O:7])[CH:3]([OH:13])[CH:2]([OH:6])[CH2:1] 5.3.1.13 phosphate aldose- [O:8][P:9](=[O:11])([OH:12])[OH:14]>>[H:21][O:7][CH:5]([H:19])[C:4](=[O:10]) ketose-isomerase [CH:3]([OH:13])[CH:2]([OH:6])[CH2:1][O:8][P:9](=[O:11])([OH:12])[OH:14] [H:21][O:9][C:3]1([H:17])[CH:4]([OH:7])[O:10][CH:6]([CH3:8])[CH:1]([OH:11]) L-Rhamnose ketol- 5.3.1.14 [CH:2]1[OH:5]>>[H:21][O:10][CH:6]([CH3:8])[CH:1]([OH:11])[CH:2]([OH:5]) isomerase [C:3](=[O:9])[CH:4]([H:17])[OH:7] [H:15][CH:7]([OH:8])[C:4]1([OH:10])[O:5][CH2:1][CH:2]([OH:9]) D-Lyxose aldose- 5.3.1.15 [CH:3]1[OH:6]>>[H:15][C:4]1([OH:10])[CH:7]([OH:8])[O:5][CH2:1][CH:2] ketose-isomerase ([OH:9])[CH:3]1[OH:6] [H:43][O:10][C:2]1([H:42])[CH:3]([OH:6])[CH:4]([O:24][CH:1]1[NH:11] N-(5'-phospho-D- [CH:12]=[N:14][c:15]2[c:16]([n:21][cH:22][n:23]2[CH:26]3[O:37][CH:29] ribosylformimino)- ([CH2:5][O:7][P:8](=[O:9])([OH:13])[OH:19])[CH:28]([OH:33])[CH:27]3[OH:35]) 5-amino-1- (5''- [C:17](=[O:20])[NH2:18])[CH2:25][O:30][P:31](=[O:32])([OH:34]) 5.3.1.16 phospho-D-ribosyl)- [OH:36]>>[H:42][O:24][CH:4]([CH2:25][O:30][P:31](=[O:32])([OH:34])[OH:36]) 4- [CH:3]([OH:6])[C:2](=[O:10])[CH:1]([H:43])[NH:11][CH:12]=[N:14][c:15]1[c:16] imidazolecarboxami ([n:21][cH:22][n:23]1[CH:26]2[O:37][CH:29]([CH2:5][O:7][P:8](=[O:9])([OH:19]) de ketol-isomerase [OH:13])[CH:28]([OH:33])[CH:27]2[OH:35])[C:17](=[O:20])[NH2:18] 5-Dehydro-4- [H:14][O:5][C:8]([H:20])([CH:9]=[O:11])[CH:7]([OH:10])[CH2:6][C:1](=[O:12]) deoxy-D- 5.3.1.17 [C:2](=[O:3])[OH:4]>>[H:14][O:11][CH:9]([H:20])[C:8](=[O:5])[CH:7]([OH:10]) glucuronate ketol- [CH2:6][C:1](=[O:12])[C:2](=[O:3])[OH:4] isomerase [H:20][C:4]1([O:7][CH:1]([OH:5])[CH:2]([OH:9])[CH:3]1[OH:6])[CH2:8] D-ribose aldose- 5.3.1.20 [OH:10]>>[H:20][CH:1]1[O:7][C:4]([OH:5])([CH2:8][OH:10])[CH:3]([OH:6]) ketose-isomerase [CH:2]1[OH:9] [H:30][O:12][CH:6]([H:29])[C:5](=[O:13])[CH:16]1[CH2:15][CH2:14] [CH:11]2[CH:10]3[CH2:9][CH2:8][C:1]4=[CH:2][C:3](=[O:7])[CH2:4][CH2:19] 11- [C:17]4([CH3:18])[CH:21]3[CH2:23][CH2:24][C:20]12[CH3:22]>>[H:30][O:13] 5.3.1.21 Deoxycorticosteron [C:5]([H:29])([CH:6]=[O:12])[CH:16]1[CH2:15][CH2:14] e ketol-isomerase [CH:11]2[CH:10]3[CH2:9][CH2:8][C:1]4=[CH:2][C:3](=[O:7])[CH2:4][CH2:19] [C:17]4([CH3:18])[CH:21]3[CH2:23][CH2:24][C:20]12[CH3:22] hydroxypyruvate [H:10][O:5][CH:6]([H:8])[C:1](=[O:7])[C:2](=[O:3])[OH:4]>>[H:10][O:7][C:1] 5.3.1.22 aldose-ketose- ([H:8])([CH:6]=[O:5])[C:2](=[O:3])[OH:4] isomerase 5-Methylthio-5- [H:23][O:9][C:2]1([H:21])[CH:3]([OH:7])[CH:4]([O:13][CH:1]1[O:8][P:10] deoxy-D-ribose-1- (=[O:11])([OH:12])[OH:15])[CH2:14][S:5][CH3:6]>>[H:21][O:13][CH:4] 5.3.1.23 phosphate ketol- ([CH2:14][S:5][CH3:6])[CH:3]([OH:7])[C:2](=[O:9])[CH:1]([H:23])[O:8][P:10] isomerase (=[O:11])([OH:15])[OH:12] [H:29][O:9][C:2]1([H:28])[CH:3]([OH:7])[CH:4]([O:8][CH:1]1[NH:11] N-(5-Phospho-beta- [c:12]2[cH:14][cH:15][cH:16][cH:21][c:20]2[C:23](=[O:5])[OH:6])[CH2:10][O:13] D- [P:17](=[O:18])([OH:19])[OH:22]>>[H:29][O:8][CH:4]([CH2:10][O:13][P:17] 5.3.1.24 ribosyl)anthranilate (=[O:18])([OH:19])[OH:22])[CH:3]([OH:7])[C:2](=[O:9])[CH:1]([H:28])[NH:11] ketol-isomerase [c:12]1[cH:14][cH:15][cH:16][cH:21][c:20]1[C:23](=[O:5])[OH:6]

[H:21][O:9][C:3]1([H:17])[CH:4]([OH:7])[O:10][CH:6]([CH3:8])[CH:1]([OH:11]) L-fucose aldose- 5.3.1.25 [CH:2]1[OH:5]>>[H:21][O:10][CH:6]([CH3:8])[CH:1]([OH:11])[CH:2]([OH:5]) ketose-isomerase [C:3](=[O:9])[CH:4]([H:17])[OH:7]

31 [H:21][C:3]1([OH:10])[CH:4]([OH:7])[O:14][CH:13]([CH2:15][O:5][P:6](=[O:8]) D-Galactose 6- ([OH:9])[OH:11])[CH:1]([OH:16])[CH:2]1[OH:12]>>[H:21][CH:4]([OH:7]) 5.3.1.26 phosphate ketol- [C:3]1([OH:10])[O:14][CH:13]([CH2:15][O:5][P:6](=[O:8])([OH:11])[OH:9]) isomerase [CH:1]([OH:16])[CH:2]1[OH:12] [H:20][O:7][CH:2]([CH2:1][O:9][P:10](=[O:11])([OH:12])[OH:15])[CH:3] D-arabino-hex-3- ([OH:16])[C:4](=[O:14])[C:5]([H:25])([OH:13])[CH2:6][OH:8]>>[H:20][O:14] 5.3.1.27 ulose-6-phosphate [C:4]1([H:25])[CH:3]([OH:16])[CH:2]([O:7][C:5]1([OH:13])[CH2:6][OH:8]) isomerase [CH2:1][O:9][P:10](=[O:11])([OH:15])[OH:12] D-glycero-D- [H:21][O:8][CH:3]([CH:2]([OH:10])[CH2:1][O:12][P:13](=[O:14])([OH:15]) manno-heptose 7- [OH:18])[CH:4]([OH:17])[CH:5]([OH:16])[C:6](=[O:11])[CH:7]([H:22]) 5.3.1.28 phosphate aldose- [OH:9]>>[H:21][O:11][C:6]1([H:22])[CH:7]([OH:9])[O:8][CH:3]([CH:2]([OH:10]) ketose-isomerase [CH2:1][O:12][P:13](=[O:14])([OH:18])[OH:15])[CH:4]([OH:17])[CH:5]1[OH:16] alpha-D-ribose 1,5- [H:22][C:4]1([O:11][CH:1]([O:8][P:9](=[O:12])([OH:14])[OH:17])[CH:2] bisphosphate ([OH:10])[CH:3]1[OH:7])[CH2:13][O:15][P:16](=[O:18])([OH:5])[OH:6]>>[H:22] 5.3.1.29 aldose-ketose- [CH:1]([O:8][P:9](=[O:12])([OH:17])[OH:14])[CH:2]([OH:10])[CH:3]([OH:7]) isomerase [C:4](=[O:11])[CH2:13][O:15][P:16](=[O:18])([OH:5])[OH:6] [H:19][CH:5]([C:1](=[O:12])[C:2](=[O:3])[OH:4])[c:6]1[cH:7][cH:8][cH:11] Phenylpyruvate 5.3.2.1 [cH:10][cH:9]1>>[H:19][O:12][C:1](=[CH:5][c:6]1[cH:7][cH:8][cH:11][cH:10] keto-enol-isomerase [cH:9]1)[C:2](=[O:3])[OH:4] Oxaloacetate keto- [H:10][O:9][C:6](=[O:7])[C:5](=[O:8])[CH:1]([H:13])[C:2](=[O:3]) 5.3.2.2 enol-isomerase [OH:4]>>[H:13][O:7][C:6](=[O:9])[C:5]([O:8][H:10])=[CH:1][C:2](=[O:3])[OH:4] [H:43][O:20][C:15]1([H:42])[C:16](=[O:17])[CH:32]([O:30][CH:9]([O:8][P:35] dTDP-4-dehydro-6- (=[O:5])([OH:7])[O:34][P:28](=[O:29])([OH:31])[O:27][CH2:26][CH:22]2[O:25] deoxy-alpha-D- [CH:18]([n:11]3[cH:1][c:2]([c:3](=[O:6])[nH:4][c:12]3=[O:14])[CH3:10])[CH2:19] glucopyranose:dTD [CH:21]2[OH:23])[CH:13]1[OH:24])[CH3:33]>>[H:42][O:17][C:16]1([H:43]) 5.3.2.3 P-3-dehydro-6- [C:15](=[O:20])[CH:13]([OH:24])[CH:9]([O:30][CH:32]1[CH3:33])[O:8][P:35] deoxy-alpha-D- (=[O:5])([OH:7])[O:34][P:28](=[O:29])([OH:31])[O:27][CH2:26][CH:22]2[O:25] galactopyranose [CH:18]([n:11]3[cH:1][c:2]([c:3](=[O:6])[nH:4][c:12]3=[O:14])[CH3:10])[CH2:19] isomerase [CH:21]2[OH:23] [H:43][O:20][C:15]1([H:42])[C:16](=[O:17])[CH:32]([O:30][CH:9]([O:8][P:35] dTDP-4-dehydro-6- (=[O:5])([OH:7])[O:34][P:28](=[O:29])([OH:31])[O:27][CH2:26][CH:22]2[O:25] deoxy-alpha-D- [CH:18]([n:11]3[cH:1][c:2]([c:3](=[O:6])[nH:4][c:12]3=[O:14])[CH3:10])[CH2:19] glucopyranose:dTD [CH:21]2[OH:23])[CH:13]1[OH:24])[CH3:33]>>[H:42][O:17][C:16]1([H:43]) 5.3.2.4 P-3-dehydro-6- [C:15](=[O:20])[CH:13]([OH:24])[CH:9]([O:30][CH:32]1[CH3:33])[O:8][P:35] deoxy-alpha-D- (=[O:5])([OH:7])[O:34][P:28](=[O:29])([OH:31])[O:27][CH2:26][CH:22]2[O:25] glucopyranose [CH:18]([n:11]3[cH:1][c:2]([c:3](=[O:6])[nH:4][c:12]3=[O:14])[CH3:10])[CH2:19] isomerase [CH:21]2[OH:23] 2,3-diketo-5- [H:19][O:11][P:9](=[O:10])([OH:14])[O:8][CH:5]([H:16])[C:4](=[O:6])[C:3] methylthiopentyl-1- 5.3.2.5 (=[O:7])[CH2:2][CH2:1][S:12][CH3:13]>>[H:19][O:6][C:4](=[CH:5][O:8][P:9] phosphate keto--- (=[O:11])([OH:14])[O:10][H:16])[C:3](=[O:7])[CH2:2][CH2:1][S:12][CH3:13] enol-isomerase [H:17][O:11][C:1](=[CH:2][CH:3]=[CH:4][C:5](=[O:6])[OH:7])[C:8](=[O:9]) 2-hydroxymuconate 5.3.2.6 [OH:10]>>[H:17][CH:2]([CH:3]=[CH:4][C:5](=[O:6])[OH:7])[C:1](=[O:11])[C:8] tautomerase (=[O:9])[OH:10] 1,5-anhydro-4- deoxy-D-glycero- [H:16][O:7][C:2]1=[CH:1][CH:10]([O:9][CH:4]([H:13])[C:3]1=[O:6])[CH2:5] 5.3.2.7 hex-3-en-2-ulose [OH:8]>>[H:16][O:6][C:3]1=[CH:4][O:9][CH:10]([CH2:5][OH:8])[CH:1]([H:13]) Delta3-Delta1- [C:2]1=[O:7] isomerase 4-oxalomesaconate [H:20][CH:11]([C:12](=[O:13])[C:14](=[O:6])[OH:7])[C:1](=[CH:2][C:3](=[O:4]) 5.3.2.8 keto---enol- [OH:5])[C:8](=[O:9])[OH:10]>>[H:20][O:13][C:12](=[CH:11][C:1](=[CH:2][C:3] isomerase (=[O:4])[OH:5])[C:8](=[O:9])[OH:10])[C:14](=[O:6])[OH:7] [H:30][CH:9]1[C:10](=[O:12])[CH2:11][CH2:17][C:13]2([C:1]1=[CH:2][CH2:3] 3-Oxo-delta5- [CH:4]3[CH:18]2[CH2:19][CH2:20][C:15]4([CH3:16])[CH2:8][CH2:7][CH2:6] 5.3.3.1 steroid delta5- [CH:5]34)[CH3:14]>>[H:30][CH:2]1[C:1]2=[CH:9][C:10](=[O:12])[CH2:11] delat4-isomerase [CH2:17][C:13]2([CH3:14])[CH:18]3[CH2:19][CH2:20][C:15]4([CH3:16])[CH2:8] [CH2:7][CH2:6][CH:5]4[CH:4]3[CH2:3]1

32 Isopentenyl- [H:24][CH:8]([C:2](=[CH2:1])[CH3:3])[CH2:9][O:10][P:11](=[O:12])([OH:14]) 5.3.3.2 diphosphate delta3- [O:4][P:5](=[O:6])([OH:7])[OH:13]>>[H:24][CH2:1][C:2](=[CH:8][CH2:9][O:10] delta2-isomerase [P:11](=[O:12])([OH:14])[O:4][P:5](=[O:6])([OH:7])[OH:13])[CH3:3] [H:90][CH:3]([CH:2]=[CH2:1])[C:4](=[O:5])[S:6][CH2:7][CH2:8][NH:11][C:12] (=[O:52])[CH2:14][CH2:15][NH:16][C:18](=[O:50])[CH:21]([OH:49])[C:23] ([CH3:24])([CH3:26])[CH2:28][O:29][P:30](=[O:32])([OH:34])[O:35][P:36] (=[O:37])([OH:40])[O:42][CH2:43][CH:44]1[O:17][CH:47]([n:19]2[cH:20][n:22] [c:25]3[c:31]([n:38][cH:41][n:39][c:27]32)[NH2:33])[CH:46]([OH:48]) Vinylacetyl-CoA [CH:45]1[O:51][P:53](=[O:9])([OH:10])[OH:13]>>[H:90][CH2:1][CH:2]=[CH:3] 5.3.3.3 delta3-delta2- [C:4](=[O:5])[S:6][CH2:7][CH2:8][NH:11][C:12](=[O:52])[CH2:14][CH2:15] isomerase [NH:16][C:18](=[O:50])[CH:21]([OH:49])[C:23]([CH3:26])([CH3:24])[CH2:28] [O:29][P:30](=[O:32])([OH:34])[O:35][P:36](=[O:37])([OH:40])[O:42][CH2:43] [CH:44]1[O:17][CH:47]([n:19]2[cH:20][n:22][c:25]3[c:31]([n:38][cH:41][n:39] [c:27]32)[NH2:33])[CH:46]([OH:48])[CH:45]1[O:51][P:53](=[O:9])([OH:10]) [OH:13]

(S)-5-oxo-2,5- [H:15][C:7]1([O:5][C:3](=[O:4])[CH:2]=[CH:1]1)[CH2:8][C:9](=[O:10]) dihydrofuran-2- 5.3.3.4 [OH:6]>>[H:15][CH:2]1[CH:1]=[C:7]([O:5][C:3]1=[O:4])[CH2:8][C:9](=[O:10]) acetate delta3- [OH:6] delat2-isomerase [H:34][C:16]12[C:1](=[CH:2][CH2:3][CH:4]3[CH2:5][CH:6]([OH:10])[CH2:7] [CH2:28][C:25]31[CH3:26])[CH:8]4[CH2:9][CH2:11][CH:12]([CH:15]([CH3:19]) 5alpha-Cholest-7- [CH2:20][CH2:21][CH2:22][CH:23]([CH3:24])[CH3:27])[C:13]4([CH3:14]) 5.3.3.5 en-3beta-ol delta7- [CH2:18][CH2:17]2>>[H:34][CH:2]1[C:1]2=[C:16]([CH2:17][CH2:18] delta8-isomerase [C:13]3([CH3:14])[CH:8]2[CH2:9][CH2:11][CH:12]3[CH:15]([CH3:19])[CH2:20] [CH2:21][CH2:22][CH:23]([CH3:24])[CH3:27])[C:25]4([CH3:26])[CH2:28] [CH2:7][CH:6]([OH:10])[CH2:5][CH:4]4[CH2:3]1 Methylitaconate [H:16][C:6]([C:7](=[O:8])[OH:10])([C:2](=[CH2:1])[C:3](=[O:4])[OH:5]) 5.3.3.6 delta2-delta3- [CH3:9]>>[H:16][CH2:1][C:2]([C:3](=[O:4])[OH:5])=[C:6]([C:7](=[O:8])[OH:10]) isomerase [CH3:9] trans-Aconitate [O:4]=[C:3]([OH:5])[CH:2]=[C:1]([C:8](=[O:10])[OH:11])[CH2:12][C:6](=[O:7]) 5.3.3.7 delta2-delta3- [OH:9]>>[O:4]=[C:3]([OH:5])[CH:2]=[C:1]([C:8](=[O:10])[OH:11])[CH2:12][C:6] isomerase (=[O:7])[OH:9] [H:94][CH:3]([CH:2]=[CH:1][CH2:49][CH2:50][CH2:52][CH2:53][CH2:54] [CH2:55][CH2:56][CH3:57])[C:4](=[O:5])[S:6][CH2:7][CH2:8][NH:11][C:12] (=[O:46])[CH2:14][CH2:15][NH:16][C:20](=[O:38])[CH:22]([OH:36])[C:25] ([CH3:26])([CH3:28])[CH2:29][O:30][P:31](=[O:32])([OH:33])[O:34][P:35] (=[O:37])([OH:39])[O:40][CH2:41][CH:42]1[O:61][CH:45]([n:9]2[cH:10][n:13] 3-cis-Dodecenoyl- [c:17]3[c:19]([n:23][cH:27][n:24][c:18]32)[NH2:21])[CH:44]([OH:47]) CoA delta3-cis- [CH:43]1[O:48][P:51](=[O:58])([OH:59])[OH:60]>>[H:94][CH:1]([CH:2]=[CH:3] 5.3.3.8 delta2-trans- [C:4](=[O:5])[S:6][CH2:7][CH2:8][NH:11][C:12](=[O:46])[CH2:14][CH2:15] isomerase [NH:16][C:20](=[O:38])[CH:22]([OH:36])[C:25]([CH3:28])([CH3:26])[CH2:29] [O:30][P:31](=[O:32])([OH:33])[O:34][P:35](=[O:37])([OH:39])[O:40][CH2:41] [CH:42]1[O:61][CH:45]([n:9]2[cH:10][n:13][c:17]3[c:19]([n:23][cH:27][n:24] [c:18]32)[NH2:21])[CH:44]([OH:47])[CH:43]1[O:48][P:51](=[O:58])([OH:59]) [OH:60])[CH2:49][CH2:50][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56] [CH3:57] [H:55][C:6]1([CH:1]=[CH:2][C:3](=[O:5])[CH:4]1[CH2:15][CH2:16][CH2:17] [CH2:18][CH2:19][CH2:20][C:22](=[O:23])[OH:24])[CH:7]=[CH:8][CH:9] prostaglandin-A1 ([OH:14])[CH2:10][CH2:11][CH2:12][CH2:13][CH3:21]>>[H:55] 5.3.3.9 Delta-isomerase [CH:2]1[CH:1]=[C:6]([CH:7]=[CH:8][CH:9]([OH:14])[CH2:10][CH2:11][CH2:12] [CH2:13][CH3:21])[CH:4]([C:3]1=[O:5])[CH2:15][CH2:16][CH2:17][CH2:18] [CH2:19][CH2:20][C:22](=[O:23])[OH:24] 5-Carboxymethyl-2- [H:23][O:15][C:1](=[CH:2][CH:3]=[C:4]([C:5](=[O:6])[OH:7])[CH2:8][C:9] hydroxymuconate (=[O:10])[OH:14])[C:11](=[O:12])[OH:13]>>[H:23][C:4]([CH:3]=[CH:2][C:1] 5.3.3.10 delta2,delta4-2- (=[O:15])[C:11](=[O:12])[OH:13])([C:5](=[O:6])[OH:7])[CH2:8][C:9](=[O:10]) oxo,delta3- [OH:14] isomerase

33 Isopiperitenone [H:13][C:4]1([C:3](=[O:7])[CH:2]=[C:1]([CH3:8])[CH2:10][CH2:11]1)[C:5] 5.3.3.11 delta8-delta4- (=[CH2:6])[CH3:9]>>[H:13][CH2:6][C:5](=[C:4]1[C:3](=[O:7])[CH:2]=[C:1] isomerase ([CH3:8])[CH2:10][CH2:11]1)[CH3:9] L-Dopachrome [H:18][CH:13]1[C:8]2=[CH:10][C:4](=[O:5])[C:3](=[O:6])[CH:2]=[C:1]2[NH:7] 5.3.3.12 delta7-delta2- [C:14]1([H:20])[C:9](=[O:11])[OH:12]>>[H:20][O:5][c:4]1[cH:10][c:8]2[cH:13] isomerase [c:14]([nH:7][c:1]2[cH:2][c:3]1[O:6][H:18])[C:9](=[O:11])[OH:12] [H:35][CH:9]([CH:8]=[CH:7][CH2:6][CH:5]=[CH:4][CH2:3][CH:2]=[CH:1] (5Z,8Z,11Z,14Z,17 [CH2:21][CH3:22])[CH:10]=[CH:11][CH:12]([H:31])[CH:13]=[CH:14][CH2:15] Z)- [CH2:16][CH2:17][C:18](=[O:19])[OH:20]>>[H:31][CH:8]([CH:9]=[CH:10] 5.3.3.13 eicosapentaenoate [CH:11]=[CH:12][CH:13]=[CH:14][CH2:15][CH2:16][CH2:17][C:18](=[O:19]) delta8,11-delta7,9- [OH:20])[CH:7]([H:35])[CH2:6][CH:5]=[CH:4][CH2:3][CH:2]=[CH:1][CH2:21] isomerase [CH3:22] decenoyl-[acyl- carrier-protein] [*:6][S:5][C:3](=[O:4])[CH:2]=[CH:1][CH:8]([H:29])[CH2:9][CH2:10][CH2:11] 5.3.3.14 Delta2-trans- [CH2:12][CH2:13][CH3:7]>>[*:6][S:5][C:3](=[O:4])[CH:2]([H:29])[CH:1]=[CH:8] Delta3-cis- [CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:7] isomerase (5S,6S)-6-amino-5- hydroxycyclohexan [H:19][O:10][C:11]1([H:18])[CH:1]=[CH:2][CH:3]=[C:4]([C:5](=[O:6])[OH:7]) 5.3.3.17 e-1,3-diene-1- [CH:8]1[NH2:9]>>[H:19][CH:1]1[CH:2]=[CH:3][C:4]([H:18])([C:5](=[O:6]) carboxyate [OH:7])[CH:8]([NH2:9])[C:11]1=[O:10] isomerase [H:97][CH:9]([C:10](=[O:11])[S:13][CH2:14][CH2:15][NH:16][C:17](=[O:55]) [CH2:18][CH2:19][NH:26][C:27](=[O:53])[CH:28]([OH:49])[C:29]([CH3:31]) ([CH3:33])[CH2:34][O:36][P:37](=[O:38])([OH:39])[O:42][P:43](=[O:44]) ([OH:45])[O:46][CH2:47][CH:48]1[O:20][CH:52]([n:21]2[cH:22][n:23] [c:24]3[c:30]([n:35][cH:41][n:40][c:25]32)[NH2:32])[CH:51]([OH:54]) 2-(1,2-epoxy-1,2- [CH:50]1[O:58][P:5](=[O:6])([OH:7])[OH:12])[C:8]45[O:57] 5.3.3.18 dihydrophenyl)acet [CH:56]5[CH:4]=[CH:3][CH:2]=[CH:1]4>>[H:97][CH:1]1[CH:2]=[CH:3] yl-CoA isomerase [CH:4]=[CH:56][O:57][C:8]1=[CH:9][C:10](=[O:11])[S:13][CH2:14][CH2:15] [NH:16][C:17](=[O:55])[CH2:18][CH2:19][NH:26][C:27](=[O:53])[CH:28] ([OH:49])[C:29]([CH3:31])([CH3:33])[CH2:34][O:36][P:37](=[O:38])([OH:39]) [O:42][P:43](=[O:44])([OH:45])[O:46][CH2:47][CH:48]2[O:20][CH:52] ([n:21]3[cH:22][n:23][c:24]4[c:30]([n:35][cH:41][n:40][c:25]43)[NH2:32])[CH:51] ([OH:54])[CH:50]2[O:58][P:5](=[O:6])([OH:12])[OH:7] (5Z,13E)-(15S)- [H:31][C:4]12[O:7][O:8][CH:6]([CH2:5]1)[CH:9]([CH2:10][CH:11]=[CH:12] 9alpha,11alpha- [CH2:13][CH2:14][CH2:15][C:22](=[O:23])[OH:24])[CH:3]2[CH:2]=[CH:1] Epidioxy-15- [CH:16]([OH:25])[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]>>[H:31][O:8] 5.3.99.2 hydroxyprosta-5,13- [CH:6]1[CH2:5][C:4](=[O:7])[CH:3]([CH:2]=[CH:1][CH:16]([OH:25])[CH2:17] dienoate D- [CH2:18][CH2:19][CH2:20][CH3:21])[CH:9]1[CH2:10][CH:11]=[CH:12][CH2:13] isomerase [CH2:14][CH2:15][C:22](=[O:23])[OH:24] (5Z,13E)-(15S)- [H:36][C:6]12[O:8][O:7][CH:4]([CH2:5]1)[CH:3]([CH:2]=[CH:1][CH:16] 9alpha,11alpha- ([OH:25])[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH:9]2[CH2:10] epidioxy-15- [CH:11]=[CH:12][CH2:13][CH2:14][CH2:15][C:22](=[O:23])[OH:24]>>[H:36] 5.3.99.3 hydroxyprosta-5,13- [O:7][CH:4]1[CH2:5][C:6](=[O:8])[CH:9]([CH2:10][CH:11]=[CH:12][CH2:13] dienoate E- [CH2:14][CH2:15][C:22](=[O:23])[OH:24])[CH:3]1[CH:2]=[CH:1][CH:16] isomerase ([OH:25])[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21] (5Z,13E)-(15S)- [H:33][C:11](=[CH:12][CH2:13][CH2:14][CH2:15][C:22](=[O:23])[OH:24]) 9alpha,11alpha- [CH2:10][CH:9]1[CH:6]2[O:8][O:7][CH:4]([CH2:5]2)[CH:3]1[CH:2]=[CH:1] Epidioxy-15- [CH:16]([OH:25])[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]>>[H:33][O:7] 5.3.99.4 hydroxyprosta-5,13- [CH:4]1[CH2:5][CH:6]2[O:8][C:11](=[CH:12][CH2:13][CH2:14][CH2:15][C:22] dienoate 6- (=[O:23])[OH:24])[CH2:10][CH:9]2[CH:3]1[CH:2]=[CH:1][CH:16]([OH:25]) isomerase [CH2:17][CH2:18][CH2:19][CH2:20][CH3:21] 5.3.99.5 (5Z,13E)-(15S)- [O:23]=[C:22]([OH:24])[CH2:15][CH2:14][CH2:13][CH:12]=[CH:11][CH2:10] 9alpha,11alpha- [CH:9]1[CH:6]2[O:8][O:7][CH:4]([CH2:5]2)[CH:3]1[CH:2]=[CH:1][CH:16] Epidioxy-15- ([OH:25])[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]>>[O:23]=[C:22] hydroxyprosta-5,13- ([OH:24])[CH2:15][CH2:14][CH2:13][CH:12]=[CH:11][CH2:10][CH:9]1[CH:3] thromboxane-A2- ([O:7][CH:4]2[O:8][CH:6]1[CH2:5]2)[CH:2]=[CH:1][CH:16]([OH:25])[CH2:17]

34 isomerase [CH2:18][CH2:19][CH2:20][CH3:21] [H:33][C:5]1([O:21][C:4]1=[CH:3][CH:2]=[CH:1][CH2:11][CH2:12][CH2:13] (9Z)-(13S)-12,13- [CH2:14][CH2:15][CH2:16][CH2:17][C:18](=[O:19])[OH:20])[CH2:6] Epoxyoctadeca- 5.3.99.6 [CH:7]=[CH:8][CH2:9][CH3:10]>>[H:33][C:4]1=[CH:3][CH:2]([CH2:11][CH2:12] 9,11,15-trienoate [CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18](=[O:19])[OH:20])[CH:1] isomerase ([C:5]1=[O:21])[CH2:6][CH:7]=[CH:8][CH2:9][CH3:10] Styrene-oxide [H:17][CH:1]1[O:9][CH:2]1[c:3]2[cH:4][cH:5][cH:6][cH:8][cH:7]2>>[H:17][CH:2] 5.3.99.7 isomerase ([CH:1]=[O:9])[c:3]1[cH:4][cH:5][cH:6][cH:8][cH:7]1 [OH:30][CH:26]1[CH2:41][C:35]2([O:44][C:19]2([CH:18]=[CH:17][C:16] (=[CH:15][CH:14]=[CH:13][C:12](=[CH:11][CH:10]=[CH:9][CH:8]=[C:7] ([CH:6]=[CH:5][CH:4]=[C:3]([CH:2]=[CH:1][C:29]34[O:43][C:39]4([CH3:40]) [CH2:42][CH:36]([OH:37])[CH2:34][C:31]3([CH3:32])[CH3:33])[CH3:28]) violaxanthin- [CH3:27])[CH3:24])[CH3:22])[C:20]([CH3:23])([CH3:21])[CH2:25]1) capsorubin 5.3.99.8 [CH3:38]>>[O:43]=[C:29]([CH:1]=[CH:2][C:3](=[CH:4][CH:5]=[CH:6][C:7] isomerase (ketone- (=[CH:8][CH:9]=[CH:10][CH:11]=[C:12]([CH:13]=[CH:14][CH:15]=[C:16] forming) ([CH:17]=[CH:18][C:19](=[O:44])[C:35]1([CH3:38])[CH2:41][CH:26]([OH:30]) [CH2:25][C:20]1([CH3:21])[CH3:23])[CH3:22])[CH3:24])[CH3:27])[CH3:28]) [C:39]2([CH3:40])[CH2:42][CH:36]([OH:37])[CH2:34][C:31]2([CH3:32]) [CH3:33] [H:100][C:1](=[CH:2][C:3](=[CH:4][CH:5]=[CH:6][C:7](=[CH:8][CH:9]=[CH:10] [CH:11]=[C:12]([CH:13]=[CH:14][CH:15]=[C:16]([CH:17]=[CH:18] [C:19]12[O:44][C:35]2([CH3:38])[CH2:41][CH:26]([OH:30])[CH2:25] [C:20]1([CH3:23])[CH3:21])[CH3:22])[CH3:24])[CH3:27])[CH3:28]) violaxanthin- [C:29]34[O:43][C:39]4([CH3:40])[CH2:42][CH:36]([OH:37])[CH2:34] neoxanthin 5.3.99.9 [C:31]3([CH3:32])[CH3:33]>>[H:100][O:43][C:39]1([C:29](=[C:1]=[CH:2][C:3] isomerase (epoxide- (=[CH:4][CH:5]=[CH:6][C:7](=[CH:8][CH:9]=[CH:10][CH:11]=[C:12] opening) ([CH:13]=[CH:14][CH:15]=[C:16]([CH:17]=[CH:18][C:19]23[O:44] [C:35]3([CH3:38])[CH2:41][CH:26]([OH:30])[CH2:25][C:20]2([CH3:21]) [CH3:23])[CH3:22])[CH3:24])[CH3:27])[CH3:28])[C:31]([CH3:32])([CH3:33]) [CH2:34][CH:36]([OH:37])[CH2:42]1)[CH3:40] 2-(2-carboxy-4- [H:24][C:7]1([N:6]=[C:3]([C:2]([S:8]1)=[CH:1][CH2:16][O:5][P:9](=[O:10]) methylthiazol-5- ([OH:12])[OH:15])[CH3:4])[C:11](=[O:13])[OH:14]>>[H:24][CH:1]([c:2]1[s:8] 5.3.99.10 yl)ethyl phosphate [c:7]([n:6][c:3]1[CH3:4])[C:11](=[O:13])[OH:14])[CH2:16][O:5][P:9](=[O:10]) isomerase ([OH:15])[OH:12] [*:18][C:1](=[O:2])[O:3][CH:4]([CH2:10][O:11][P:12](=[O:13])([OH:14])[O:17] [CH2:19][CH2:6][N+:7]([CH3:8])([CH3:15])[CH3:16])[CH:5]([H:23]) Lysolecithin 2,3- 5.4.1.1 [OH:9]>>[*:18][C:1](=[O:2])[O:3][CH:4]([H:23])[CH:5]([OH:9])[CH2:10][O:11] acylmutase [P:12](=[O:13])([OH:14])[O:17][CH2:19][CH2:6][N+:7]([CH3:8])([CH3:15]) [CH3:16] [H:21][O:12][CH2:5][CH:4]1[O:7][CH:6]([O:8][P:9](=[O:10])([OH:11])[OH:13]) alpha-D-glucose [CH:1]([OH:16])[CH:2]([OH:15])[CH:3]1[OH:14]>>[H:21][O:8][CH:6]1[O:7] 5.4.2.2 1,6-phosphomutase [CH:4]([CH2:5][O:12][P:9](=[O:10])([OH:11])[OH:13])[CH:3]([OH:14])[CH:2] ([OH:15])[CH:1]1[OH:16] [H:22][O:7][CH:4]1[O:17][CH:5]([CH2:6][O:8][P:9](=[O:11])([OH:12])[OH:15]) N-Acetyl-D- [CH:1]([OH:19])[CH:2]([OH:18])[CH:3]1[NH:10][C:13](=[O:16]) glucosamine 1- 5.4.2.3 [CH3:14]>>[H:22][O:8][CH2:6][CH:5]1[O:17][CH:4]([O:7][P:9](=[O:11]) phosphate 1,6- ([OH:12])[OH:15])[CH:3]([NH:10][C:13](=[O:16])[CH3:14])[CH:2]([OH:18]) phosphomutase [CH:1]1[OH:19] 3-phospho-D- [H:23][O:14][CH:1]([C:2](=[O:3])[O:4][P:5](=[O:6])([OH:7])[OH:10])[CH2:12] 5.4.2.4 glycerate 1,2- [O:13][P:15](=[O:8])([OH:9])[OH:11]>>[H:23][O:4][C:2](=[O:3])[CH:1]([O:14] phosphomutase [P:5](=[O:6])([OH:7])[OH:10])[CH2:12][O:13][P:15](=[O:8])([OH:11])[OH:9] [H:21][O:12][CH2:5][CH:4]1[O:7][CH:6]([O:8][P:9](=[O:10])([OH:11])[OH:13]) alpha-D-glucose [CH:1]([OH:16])[CH:2]([OH:15])[CH:3]1[OH:14]>>[H:21][O:8][CH:6]1[O:7] 5.4.2.5 1,6-phosphomutase [CH:4]([CH2:5][O:12][P:9](=[O:10])([OH:11])[OH:13])[CH:3]([OH:14])[CH:2] ([OH:15])[CH:1]1[OH:16] 5.4.2.6 beta-D-Glucose 1- [H:21][O:12][CH2:5][CH:4]1[O:7][CH:6]([O:8][P:9](=[O:10])([OH:11])[OH:13]) phosphate 1,6- [CH:1]([OH:16])[CH:2]([OH:15])[CH:3]1[OH:14]>>[H:21][O:8][CH:6]1[O:7]

35 [CH:4]([CH2:5][O:12][P:9](=[O:10])([OH:11])[OH:13])[CH:3]([OH:14])[CH:2] phosphomutase ([OH:15])[CH:1]1[OH:16] [H:17][O:5][CH2:13][CH:4]1[O:12][CH:1]([O:7][P:8](=[O:9])([OH:11])[OH:14]) D-Ribose 1,5- 5.4.2.7 [CH:2]([OH:10])[CH:3]1[OH:6]>>[H:17][O:7][CH:1]1[O:12][CH:4]([CH2:13] phosphomutase [O:5][P:8](=[O:9])([OH:11])[OH:14])[CH:3]([OH:6])[CH:2]1[OH:10] [H:19][O:7][CH:4]1[O:14][CH:13]([CH2:15][O:5][P:6](=[O:8])([OH:9])[OH:11]) D-mannose 6- [CH:1]([OH:16])[CH:2]([OH:12])[CH:3]1[OH:10]>>[H:19][O:5][CH2:15] 5.4.2.8 phosphate 1,6- [CH:13]1[O:14][CH:4]([O:7][P:6](=[O:8])([OH:11])[OH:9])[CH:3]([OH:10]) phosphomutase [CH:2]([OH:12])[CH:1]1[OH:16] phosphoenolpyruvat [O:4]=[C:3]([OH:5])[C:2]([O:6][P:7](=[O:8])([OH:9]) 5.4.2.9 e 2,3- [OH:10])=[CH2:1]>>[O:4]=[C:3]([OH:5])[C:2](=[O:6])[CH2:1][P:7](=[O:8]) phosphonomutase ([OH:10])[OH:9] [H:21][O:12][CH2:5][CH:4]1[O:7][CH:6]([O:8][P:9](=[O:10])([OH:11])[OH:13]) D-Glucosamine 1- [CH:1]([NH2:16])[CH:2]([OH:15])[CH:3]1[OH:14]>>[H:21][O:8][CH:6]1[O:7] 5.4.2.10 phosphate 1,6- [CH:4]([CH2:5][O:12][P:9](=[O:10])([OH:13])[OH:11])[CH:3]([OH:14])[CH:2] phosphomutase ([OH:15])[CH:1]1[NH2:16] [H:16][O:10][CH2:8][CH:1]([O:5][P:6](=[O:7])([OH:9])[OH:11])[C:2](=[O:3]) D-phosphoglycerate 5.4.2.11 [OH:4]>>[H:16][O:5][CH:1]([C:2](=[O:3])[OH:4])[CH2:8][O:10][P:6](=[O:7]) 2,3-phosphomutase ([OH:11])[OH:9] [H:16][O:10][CH2:8][CH:1]([O:5][P:6](=[O:7])([OH:9])[OH:11])[C:2](=[O:3]) D-phosphoglycerate 5.4.2.12 [OH:4]>>[H:16][O:5][CH:1]([C:2](=[O:3])[OH:4])[CH2:8][O:10][P:6](=[O:7]) 2,3-phosphomutase ([OH:11])[OH:9] [H:20][CH:5]([CH2:6][CH2:7][CH2:9][NH2:8])[CH:1]([NH2:10])[C:2](=[O:3]) L-Lysine 2,3- 5.4.3.2 [OH:4]>>[H:20][CH:1]([C:2](=[O:3])[OH:4])[CH:5]([NH2:10])[CH2:6][CH2:7] aminomutase [CH2:9][NH2:8] (3S)-3,6- [H:16][CH:7]([CH2:9][NH2:8])[CH2:6][CH:5]([NH2:10])[CH2:1][C:2](=[O:3]) 5.4.3.3 diaminohexanoate [OH:4]>>[H:16][CH2:9][CH:7]([NH2:8])[CH2:6][CH:5]([NH2:10])[CH2:1][C:2] 5,6-aminomutase (=[O:3])[OH:4] D-2,6- [H:16][CH:7]([CH2:9][NH2:8])[CH2:6][CH2:5][CH:1]([NH2:10])[C:2](=[O:3]) Diaminohexanoic 5.4.3.4 [OH:4]>>[H:16][CH2:9][CH:7]([NH2:8])[CH2:6][CH2:5][CH:1]([NH2:10])[C:2] acid 5,6- (=[O:3])[OH:4] aminomutase [H:15][CH:6]([CH2:8][NH2:7])[CH2:5][CH:1]([NH2:9])[C:2](=[O:3]) D-ornithine 4,5- 5.4.3.5 [OH:4]>>[H:15][CH2:8][CH:6]([NH2:7])[CH2:5][CH:1]([NH2:9])[C:2](=[O:3]) aminomutase [OH:4] [H:20][CH:5]([c:6]1[cH:7][cH:8][c:9]([OH:12])[cH:11][cH:10]1)[CH:1]([NH2:13]) L-Tyrosine 2,3- 5.4.3.6 [C:2](=[O:3])[OH:4]>>[H:20][CH:1]([C:2](=[O:3])[OH:4])[CH:5]([NH2:13]) aminomutase [c:6]1[cH:7][cH:8][c:9]([OH:12])[cH:11][cH:10]1 [H:18][CH:5]([CH:1]([NH2:9])[C:2](=[O:3])[OH:4])[CH:6]([CH3:7]) (2S)-alpha-leucine 5.4.3.7 [CH3:8]>>[H:18][CH:1]([C:2](=[O:3])[OH:4])[CH:5]([NH2:9])[CH:6]([CH3:8]) 2,3-aminomutase [CH3:7] (S)-4-Amino-5- [H:10][CH:8]([NH2:7])[C:6](=[O:9])[CH2:5][CH2:1][C:2](=[O:3])[OH:4]>>[H:10] 5.4.3.8 oxopentanoate 4,5- [C:6]([NH2:7])([CH:8]=[O:9])[CH2:5][CH2:1][C:2](=[O:3])[OH:4] aminomutase [H:16][CH:5]([CH2:6][C:7](=[O:8])[OH:10])[CH:1]([NH2:9])[C:2](=[O:3]) L-glutamate 2,3- 5.4.3.9 [OH:4]>>[H:16][CH:1]([C:2](=[O:3])[OH:4])[CH:5]([NH2:9])[CH2:6][C:7] aminomutase (=[O:8])[OH:10] L-phenylalanine 2,3-aminomutase [H:19][CH:5]([c:6]1[cH:7][cH:8][cH:11][cH:10][cH:9]1)[CH:1]([NH2:12])[C:2] 5.4.3.10 [(R)-3-amino-3- (=[O:3])[OH:4]>>[H:19][CH:1]([C:2](=[O:3])[OH:4])[CH:5]([NH2:12]) phenylpropanoate [c:6]1[cH:7][cH:8][cH:11][cH:10][cH:9]1 forming] 5.4.3.11 L-phenylalanine [H:19][CH:5]([c:6]1[cH:7][cH:8][cH:11][cH:10][cH:9]1)[CH:1]([NH2:12])[C:2] 2,3-aminomutase (=[O:3])[OH:4]>>[H:19][CH:1]([C:2](=[O:3])[OH:4])[CH:5]([NH2:12]) [(S)-3-amino-3- [c:6]1[cH:7][cH:8][cH:11][cH:10][cH:9]1

36 phenylpropanoate] (hydroxyamino)ben [H:14][NH:6][c:8]1[cH:5][cH:4][cH:3][cH:2][c:1]1[OH:7]>>[H:14][c:1]1[cH:2] 5.4.4.1 zene [cH:3][cH:4][cH:5][c:8]1[NH:6][OH:7] hydroxymutase [O:14]=[C:11]([OH:15])[C:6]([O:5][CH:12]1[CH:1]=[C:2]([CH:3]=[CH:4] chorismate [CH:13]1[OH:16])[C:7](=[O:9])[OH:10])=[CH2:8]>>[O:14]=[C:11]([OH:15])[C:6] 5.4.4.2 hydroxymutase ([O:5][CH:12]1[CH:13]=[CH:4][CH:3]=[C:2]([C:7](=[O:9])[OH:10]) [CH:1]1[OH:16])=[CH2:8] 3- [H:11][c:4]1[cH:3][cH:2][c:1]([OH:8])[cH:7][c:9]1[NH:5][OH:6]>>[H:11][NH:5] 5.4.4.3 (hydroxyamino)phe [c:9]1[cH:7][c:1]([OH:8])[cH:2][cH:3][c:4]1[OH:6] nol hydroxymutase [OH:10][CH2:7][CH:6]=[C:5]([CH3:8])[CH2:4][CH2:3][CH:2]=[C:1]([CH3:9]) geraniol 5.4.4.4 [CH3:11]>>[OH:10][C:5]([CH:6]=[CH2:7])([CH3:8])[CH2:4][CH2:3][CH:2]=[C:1] hydroxymutase ([CH3:11])[CH3:9] (8R,9Z,12Z)-8- hydroperoxyoctadec a-9,12-dienoate [H:24][CH:9]([CH2:10][CH2:11][CH2:12][C:13](=[O:14])[OH:15])[CH2:8] hydroxymutase [CH2:7][CH:6]([O:16][OH:17])[CH:5]=[CH:4][CH2:3][CH:2]=[CH:1][CH2:18] 5.4.4.5 [(5S,8R,9Z,12Z)- [CH2:19][CH2:20][CH2:21][CH3:22]>>[H:24][O:16][CH:6]([CH:5]=[CH:4] 5,8- [CH2:3][CH:2]=[CH:1][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH2:7] dihydroxyoctadeca- [CH2:8][CH:9]([OH:17])[CH2:10][CH2:11][CH2:12][C:13](=[O:14])[OH:15] 9,12-dienoate- forming] (8R,9Z,12Z)-8- hydroperoxyoctadec a-9,12-dienoate [H:28][CH:7]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13](=[O:14]) hydroxymutase [OH:15])[CH:6]([O:16][OH:17])[CH:5]=[CH:4][CH2:3][CH:2]=[CH:1][CH2:18] 5.4.4.6 [(7S,8S,9Z,12Z)- [CH2:19][CH2:20][CH2:21][CH3:22]>>[H:28][O:16][CH:6]([CH:5]=[CH:4] 7,8- [CH2:3][CH:2]=[CH:1][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH:7] dihydroxyoctadeca- ([OH:17])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13](=[O:14])[OH:15] 9,12-dienoate- forming] L-threo-3- [H:14][CH2:5][CH:6]([C:7](=[O:8])[OH:9])[CH:1]([NH2:10])[C:2](=[O:3]) Methylaspartate 5.4.99.1 [OH:4]>>[H:14][CH:6]([CH2:5][C:7](=[O:8])[OH:9])[CH:1]([NH2:10])[C:2] carboxy- (=[O:3])[OH:4] aminomethylmutase [H:94][CH2:54][CH:1]([C:2](=[O:3])[OH:4])[C:6](=[O:7])[S:8][CH2:9][CH2:11] [NH:12][C:14](=[O:52])[CH2:15][CH2:16][NH:18][C:21](=[O:51])[CH:24] ([OH:50])[C:25]([CH3:26])([CH3:28])[CH2:30][O:31][P:33](=[O:34])([OH:35]) [O:36][P:38](=[O:41])([OH:42])[O:43][CH2:44][CH:45]1[O:17][CH:48] ([n:19]2[cH:20][n:22][c:23]3[c:29]([n:37][cH:40][n:39][c:27]32)[NH2:32])[CH:47] (R)-Methylmalonyl- ([OH:49])[CH:46]1[O:53][P:55](=[O:5])([OH:10])[OH:13]>>[H:94][CH:1]([C:6] 5.4.99.2 CoA CoA- (=[O:7])[S:8][CH2:9][CH2:11][NH:12][C:14](=[O:52])[CH2:15][CH2:16][NH:18] carbonylmutase [C:21](=[O:51])[CH:24]([OH:50])[C:25]([CH3:28])([CH3:26])[CH2:30][O:31] [P:33](=[O:34])([OH:35])[O:36][P:38](=[O:41])([OH:42])[O:43][CH2:44] [CH:45]1[O:17][CH:48]([n:19]2[cH:20][n:22][c:23]3[c:29]([n:37][cH:40][n:39] [c:27]32)[NH2:32])[CH:47]([OH:49])[CH:46]1[O:53][P:55](=[O:5])([OH:10]) [OH:13])[CH2:54][C:2](=[O:3])[OH:4] 2-Acetolactate [H:17][O:9][C:1]([C:2](=[O:3])[OH:4])([C:5](=[O:6])[CH3:8])[CH3:7]>>[H:17] 5.4.99.3 methylmutase [O:6][C:5]([C:1](=[O:9])[C:2](=[O:3])[OH:4])([CH3:7])[CH3:8] 2- methyleneglutarate [H:16][CH:7]([C:2](=[CH2:1])[C:3](=[O:4])[OH:5])[CH2:8][C:9](=[O:10]) 5.4.99.4 carboxy- [OH:6]>>[H:16][CH2:8][CH:7]([C:9](=[O:10])[OH:6])[C:2](=[CH2:1])[C:3] methylenemethylmu (=[O:4])[OH:5] tase 5.4.99.5 Chorismate [O:14]=[C:11]([OH:15])[C:6]([O:5][CH:12]1[CH:1]=[C:2]([CH:3]=[CH:4] pyruvatemutase [CH:13]1[OH:16])[C:7](=[O:9])[OH:10])=[CH2:8]>>[O:14]=[C:11]([OH:15])[C:6]

37 (=[O:5])[CH2:8][C:2]1([CH:1]=[CH:12][CH:13]([OH:16])[CH:4]=[CH:3]1)[C:7] (=[O:9])[OH:10] [H:59][C:10](=[C:9]([CH3:24])[CH2:8][CH2:7][CH:6]=[C:5]([CH3:26])[CH2:4] [CH2:3][CH:2]=[C:1]([CH3:28])[CH3:30])[CH2:11][CH2:12][C:13] (S)-2,3- ([H:54])=[C:14]([CH3:15])[CH2:16][CH2:17][CH:19]=[C:20]([CH3:21])[CH2:23] Epoxysqualene [CH2:25][CH:27]1[O:22][C:29]1([CH3:18])[CH3:31]>>[H:59][O:22] 5.4.99.7 mutase (cyclizing, [CH:27]1[CH2:25][CH2:23][C:20]2([C:13]3=[C:14]([CH2:16][CH2:17] lanosterol-forming) [CH:19]2[C:29]1([CH3:31])[CH3:18])[C:9]4([CH3:24])[CH2:8][CH2:7][CH:6] ([C:5]([H:54])([CH3:26])[CH2:4][CH2:3][CH:2]=[C:1]([CH3:28])[CH3:30]) [C:10]4([CH3:15])[CH2:11][CH2:12]3)[CH3:21] [H:59][C:10](=[C:9]([CH3:24])[CH2:8][CH2:7][CH:6]=[C:5]([CH3:26])[CH2:4] [CH2:3][CH:2]=[C:1]([CH3:28])[CH3:30])[CH2:11][CH2:12][C:13] (S)-2,3- ([H:54])=[C:14]([CH3:15])[CH2:16][CH2:17][CH:19]=[C:20]([CH2:21][H:44]) Epoxysqualene [CH2:23][CH2:25][CH:27]1[O:22][C:29]1([CH3:18])[CH3:31]>>[H:59][O:22] 5.4.99.8 mutase (cyclizing, [CH:27]1[CH2:25][CH2:23][C:20]23[CH2:21][C:13]43[CH2:12][CH2:11] cycloartenol- [C:10]5([CH3:15])[CH:6]([CH2:7][CH2:8][C:9]5([CH3:24])[C:14]4([H:54]) forming) [CH2:16][CH2:17][CH:19]2[C:29]1([CH3:18])[CH3:31])[C:5]([H:44])([CH3:26]) [CH2:4][CH2:3][CH:2]=[C:1]([CH3:28])[CH3:30] [H:41][O:17][CH:15]1[CH:13]([OH:19])[CH:7]([OH:27])[CH:6]([O:29] [CH:30]1[CH2:32][OH:36])[O:5][P:33](=[O:34])([OH:35])[O:31][P:25](=[O:26]) ([OH:28])[O:24][CH:23]([H:51])[CH:18]2[O:22][CH:12]([n:9]3[cH:1][cH:2][c:3] UDP-alpha-D- (=[O:8])[nH:4][c:10]3=[O:11])[CH:14]([OH:21])[CH:16]2[OH:20]>>[H:51][O:24] 5.4.99.9 galactopyranose [CH:23]([CH2:32][OH:36])[CH:18]1[O:22][CH:12]([O:5][P:33](=[O:34])([OH:35]) furanomutase [O:31][P:25](=[O:26])([OH:28])[O:17][CH:15]([H:41])[CH:30]2[O:29][CH:6] ([n:9]3[cH:1][cH:2][c:3](=[O:8])[nH:4][c:10]3=[O:11])[CH:7]([OH:27]) [CH:13]2[OH:19])[CH:14]([OH:21])[CH:16]1[OH:20] [H:41][O:21][CH2:17][CH:9]1[O:16][C:20]([O:19][CH:15]2[O:18][CH:4]([CH2:5] [OH:10])[CH:3]([OH:12])[CH:2]([OH:14])[CH:1]2[OH:23])([CH2:22][OH:6]) Sucrose 5.4.99.11 [CH:7]([OH:13])[CH:8]1[OH:11]>>[H:41][O:19][C:20]1([O:16][CH:9]([CH2:17] glucosylmutase [O:21][CH:15]2[O:18][CH:4]([CH2:5][OH:10])[CH:3]([OH:12])[CH:2]([OH:14]) [CH:1]2[OH:23])[CH:8]([OH:11])[CH:7]1[OH:13])[CH2:22][OH:6] [*:39][CH:33]1[O:38][CH:26]([CH2:23][O:21][P:18](=[O:19])([OH:20])[O:17] [CH:15]2[CH:14]([OH:43])[CH:12]([O:45][CH:16]2[CH2:46][O:5][P:6](=[O:7]) ([OH:13])[O:22][CH:24]3[CH:25]([OH:32])[CH:27]([*:31])[O:29] [CH:34]3[CH2:36][O:40][P:41](=[O:42])([OH:44])[OH:47])[n:9]4[cH:1][c:2] ([H:49])[c:3](=[O:8])[nH:4][c:10]4=[O:11])[CH:28]([OH:37]) tRNA-uridine 5.4.99.12 [CH:30]1[OH:35]>>[*:39][CH:33]1[O:38][CH:26]([CH2:23][O:21][P:18](=[O:19]) uracilmutase ([OH:20])[O:17][CH:15]2[CH:14]([OH:43])[CH:12]([O:45][CH:16]2[CH2:46] [O:5][P:6](=[O:7])([OH:13])[O:22][CH:24]3[CH:25]([OH:32])[CH:27]([*:31]) [O:29][CH:34]3[CH2:36][O:40][P:41](=[O:42])([OH:47])[OH:44])[c:2]4[cH:1] [n:9]([H:49])[c:10](=[O:11])[nH:4][c:3]4=[O:8])[CH:28]([OH:37]) [CH:30]1[OH:35] [H:94][CH2:52][CH:1]([C:2](=[O:3])[S:4][CH2:5][CH2:6][NH:8][C:9](=[O:48]) [CH2:10][CH2:11][NH:12][C:15](=[O:46])[CH:18]([OH:44])[C:21]([CH3:22]) ([CH3:24])[CH2:26][O:27][P:28](=[O:29])([OH:31])[O:32][P:33](=[O:35]) ([OH:37])[O:38][CH2:39][CH:40]1[O:13][CH:43]([n:14]2[cH:16][n:17] [c:19]3[c:23]([n:30][cH:36][n:34][c:20]32)[NH2:25])[CH:42]([OH:45]) 2-Methylpropanoyl- [CH:41]1[O:47][P:49](=[O:51])([OH:53])[OH:7])[CH3:50]>>[H:94][CH:1]([C:2] 5.4.99.13 CoA CoA- (=[O:3])[S:4][CH2:5][CH2:6][NH:8][C:9](=[O:48])[CH2:10][CH2:11][NH:12] carbonylmutase [C:15](=[O:46])[CH:18]([OH:44])[C:21]([CH3:24])([CH3:22])[CH2:26][O:27] [P:28](=[O:29])([OH:31])[O:32][P:33](=[O:35])([OH:37])[O:38][CH2:39] [CH:40]1[O:13][CH:43]([n:14]2[cH:16][n:17][c:19]3[c:23]([n:30][cH:36][n:34] [c:20]32)[NH2:25])[CH:42]([OH:45])[CH:41]1[O:47][P:49](=[O:51])([OH:7]) [OH:53])[CH2:52][CH3:50] 4-Carboxymethyl-4- [H:19][C:1]1=[CH:2][C:3](=[O:4])[O:5][C:7]1([CH3:11])[CH2:6][C:8](=[O:9]) 5.4.99.14 methylbut-2-en-1,4- [OH:10]>>[H:19][C:7]1([O:5][C:3](=[O:4])[CH:2]=[C:1]1[CH3:11])[CH2:6][C:8] olide methylmutase (=[O:9])[OH:10] 5.4.99.16 Maltose alpha-D- [OH:9][CH2:5][CH:4]1[O:17][CH:15]([O:18][CH:19]2[CH:21]([OH:10])[CH:23] glucosylmutase ([OH:8])[CH:6]([OH:7])[O:20][CH:13]2[CH2:14][OH:16])[CH:1]([OH:22])[CH:2]

38 ([OH:12])[CH:3]1[OH:11]>>[OH:9][CH2:5][CH:4]1[O:17][CH:15]([O:18] [CH:19]2[O:20][CH:13]([CH2:14][OH:16])[CH:6]([OH:7])[CH:23]([OH:8]) [CH:21]2[OH:10])[CH:1]([OH:22])[CH:2]([OH:12])[CH:3]1[OH:11] [H:36][CH2:16][C:30](=[CH:28][CH2:26][CH2:24][C:21](=[CH:20][CH2:18] [CH2:17][C:14](=[CH:13][CH2:12][CH2:11][CH:10]=[C:9]([CH3:23])[CH2:8] [CH2:7][CH:6]=[C:5]([CH3:25])[CH2:4][CH2:3][CH:2]=[C:1]([CH3:27]) squalene mutase [CH3:29])[CH3:15])[CH3:22])[CH3:19]>>[H:36][CH:2]1[CH2:3][CH2:4] 5.4.99.17 (cyclizing) [C:5]2([CH3:25])[CH:6]([CH2:7][CH2:8][C:9]3([CH3:23])[CH:10]2[CH2:11] [CH2:12][CH:13]4[C:21]5([CH3:22])[CH2:24][CH2:26][CH:28]([C:30] (=[CH2:16])[CH3:19])[CH:20]5[CH2:18][CH2:17][C:14]43[CH3:15]) [C:1]1([CH3:27])[CH3:29] [H:34][c:15]1[n:12][cH:11][n:10]([c:16]1[NH:18][C:19](=[O:20])[OH:22]) 5-carboxyamino-1- [CH:1]2[O:5][CH:4]([CH2:7][O:9][P:13](=[O:14])([OH:17])[OH:21])[CH:3] (5-phospho-D- 5.4.99.18 ([OH:6])[CH:2]2[OH:8]>>[H:34][NH:18][c:16]1[c:15]([n:12][cH:11] ribosyl)imidazole [n:10]1[CH:1]2[O:5][CH:4]([CH2:7][O:9][P:13](=[O:14])([OH:21])[OH:17]) carboxymutase [CH:3]([OH:6])[CH:2]2[OH:8])[C:19](=[O:20])[OH:22] [H:41][O:19][CH:17]1[CH2:32][O:31][CH:12]([O:6][P:33](=[O:34])([OH:5]) [O:30][P:26](=[O:27])([OH:28])[O:25][CH2:23][CH:18]2[O:22][CH:11] ([n:8]3[cH:1][cH:2][c:3](=[O:7])[nH:4][c:9]3=[O:10])[CH:13]([OH:21]) UDP-L- [CH:16]2[OH:20])[CH:14]([OH:29])[CH:15]1[OH:24]>>[H:41][O:25][CH2:23] 5.4.99.30 arabinopyranose [CH:18]1[O:22][CH:11]([O:6][P:33](=[O:34])([OH:5])[O:30][P:26](=[O:27]) furanomutase ([OH:28])[O:31][CH2:32][CH:17]2[O:19][CH:12]([n:8]3[cH:1][cH:2][c:3](=[O:7]) [nH:4][c:9]3=[O:10])[CH:14]([OH:29])[CH:15]2[OH:24])[CH:13]([OH:21]) [CH:16]1[OH:20] [H:59][C:10](=[C:9]([CH3:24])[CH2:8][CH2:7][CH:6]=[C:5]([CH3:26])[CH2:4] [CH2:3][CH:2]=[C:1]([CH3:28])[CH3:30])[CH2:11][CH2:12][C:13] (S)-2,3- ([H:54])=[C:14]([CH3:15])[CH2:16][CH2:17][CH:19]=[C:20]([CH3:21])[CH2:23] epoxysqualene [CH2:25][CH:27]1[O:22][C:29]1([CH3:18])[CH3:31]>>[H:59][O:22] 5.4.99.31 mutase (cyclizing, [CH:27]1[CH2:25][CH2:23][C:20]2([C:13]3=[C:14]([CH2:16][CH2:17] thalianol-forming) [CH:19]2[C:29]1([CH3:18])[CH3:31])[C:10]([CH3:15])([CH2:11][CH2:12]3)[C:9] ([H:54])([CH3:24])[CH2:8][CH2:7][CH:6]=[C:5]([CH3:26])[CH2:4][CH2:3] [CH:2]=[C:1]([CH3:30])[CH3:28])[CH3:21] [H:67][C:6](=[C:5]([CH3:26])[CH2:4][CH2:3][CH:2]=[C:1]([CH3:28])[CH3:30]) (S)-2,3- [CH2:7][CH2:8][C:9](=[CH:10][CH2:11][CH2:12][CH:13]=[C:14]([CH3:15]) epoxysqualene [CH2:16][CH2:17][CH:19]=[C:20]([CH3:21])[CH2:23][CH2:25][CH:27]1[O:22] mutase [cyclizing, [C:29]1([CH3:18])[CH3:31])[CH3:24]>>[H:67][O:22][CH:27]1[CH2:25][CH2:23] 5.4.99.32 (17Z)-protosta- [C:20]2([CH3:21])[CH:19]([CH2:17][CH2:16][C:14]3([CH3:15]) 17(20),24-dien- [CH:13]2[CH2:12][CH2:11][CH:10]4[C:6](=[C:5]([CH3:26])[CH2:4][CH2:3] 3beta-ol-forming] [CH:2]=[C:1]([CH3:30])[CH3:28])[CH2:7][CH2:8][C:9]43[CH3:24]) [C:29]1([CH3:18])[CH3:31] [H:59][C:10](=[C:9]([CH3:24])[CH2:8][CH2:7][CH:6]=[C:5]([CH3:26])[CH2:4] [CH2:3][CH:2]=[C:1]([CH3:28])[CH3:30])[CH2:11][CH2:12][C:13] (S)-2,3- ([H:54])=[C:14]([CH3:15])[CH2:16][CH:17]([H:51])[C:19]([H:49])=[C:20] epoxysqualene ([CH3:21])[CH2:23][CH2:25][CH:27]1[O:22][C:29]1([CH3:18])[CH3:31]>>[H:59] 5.4.99.33 mutase (cyclizing, [O:22][CH:27]1[CH2:25][CH2:23][C:20]2([H:54])[C:19](=[CH:17][CH2:16] cucurbitadienol- [C:14]3([H:51])[C:13]2([CH3:15])[CH2:12][CH2:11][C:10]4([CH3:21])[CH:6] forming) ([CH2:7][CH2:8][C:9]34[CH3:24])[C:5]([H:49])([CH3:26])[CH2:4][CH2:3] [CH:2]=[C:1]([CH3:30])[CH3:28])[C:29]1([CH3:31])[CH3:18] [H:67][C:6](=[C:5]([CH3:26])[CH2:4][C:3]([H:73])([H:74])[CH:2]=[C:1] ([CH3:28])[CH3:30])[CH2:7][CH2:8][C:9](=[CH:10][CH2:11][CH2:12] (S)-2,3- [CH:13]=[C:14]([CH3:15])[CH2:16][CH2:17][CH:19]=[C:20]([CH3:21])[CH2:23] epoxysqualene [CH2:25][CH:27]1[O:22][C:29]1([CH3:18])[CH3:31])[CH3:24]>>[H:73][O:22] 5.4.99.34 mutase (cyclizing, [CH:27]1[CH2:25][CH2:23][C:20]2([CH3:21])[CH:19]([CH2:17][CH2:16] germanicol- [C:14]3([CH3:15])[CH:13]2[CH2:12][CH2:11][CH:10]4[C:1]5=[CH:2][C:3] forming) ([CH3:28])([CH3:30])[CH2:4][C:5]([H:74])([H:67])[C:6]5([CH3:26])[CH2:7] [CH2:8][C:9]43[CH3:24])[C:29]1([CH3:31])[CH3:18] 5.4.99.35 (S)-2,3- [H:59][C:10](=[C:9]([CH3:24])[CH2:8][C:7]([H:65])([H:66])[CH:6]=[C:5] epoxysqualene ([CH3:26])[C:4]([H:71])([H:72])[CH2:3][CH:2]=[C:1]([CH3:28])[CH3:30]) mutase (cyclizing, [CH2:11][CH2:12][CH:13]=[C:14]([CH3:15])[CH2:16][CH2:17][CH:19]=[C:20]

39 ([CH3:21])[CH2:23][CH2:25][CH:27]1[O:22][C:29]1([CH3:18])[CH3:31]>>[H:71] [O:22][CH:27]1[CH2:25][CH2:23][C:20]2([CH3:21])[CH:13]3[CH2:12][CH2:11] taraxerol-forming) [C:10]4([C:1](=[CH:2][CH2:3][C:4]5([CH3:28])[C:5]([H:72])([H:65])[CH:6] ([H:66])[C:7]([CH3:30])([CH3:24])[CH2:8][C:9]45[H:59])[C:14]3([CH3:15]) [CH2:16][CH2:17][CH:19]2[C:29]1([CH3:31])[CH3:18])[CH3:26] [H:49][C:19](=[C:20]([CH3:21])[CH2:23][CH2:25][CH:27]1[O:22] [C:29]1([CH3:18])[CH3:31])[CH2:17][CH2:16][C:14](=[CH:13][CH2:12][C:11] (S)-2,3- ([H:57])([H:58])[CH:10]=[C:9]([CH3:24])[C:8]([H:63])([H:64])[CH2:7] epoxysqualene [CH:6]=[C:5]([CH3:26])[C:4]([H:71])([H:72])[CH2:3][CH:2]=[C:1]([CH3:28]) 5.4.99.36 mutase (cyclizing, [CH3:30])[CH3:15]>>[H:71][O:22][CH:27]1[CH2:25][CH2:23] isomultiflorenol- [C:20]2([C:19]3=[C:4]([CH2:3][CH:2]([H:72])[C:1]2([H:63])[C:29]1([CH3:31]) forming) [CH3:18])[C:5]4([CH3:26])[CH:6]([H:64])[CH2:7][C:8]5([CH3:28])[C:9]([H:57]) ([H:58])[CH:10]([H:49])[C:11]([CH3:24])([CH3:30])[CH2:12] [CH:13]5[C:14]4([CH3:15])[CH2:16][CH2:17]3)[CH3:21] [H:43][CH2:22][C:21](=[CH:20][CH2:18][CH2:17][C:14](=[CH:13][CH2:12] [CH2:11][CH:10]=[C:9]([CH3:23])[CH2:8][CH2:7][CH:6]=[C:5]([CH3:25]) squalene mutase [CH2:4][CH2:3][CH:2]=[C:1]([CH3:27])[CH3:29])[CH3:15])[CH2:24][CH2:26] (cyclizing, [CH:28]=[C:30]([CH3:16])[CH3:19]>>[H:43][CH:2]1[CH2:3][CH2:4] 5.4.99.37 dammara-20,24- [C:5]2([CH3:25])[CH:6]([CH2:7][CH2:8][C:9]3([CH3:23])[CH:10]2[CH2:11] diene-forming) [CH2:12][CH:13]4[CH:20]([C:21](=[CH2:22])[CH2:24][CH2:26][CH:28]=[C:30] ([CH3:19])[CH3:16])[CH2:18][CH2:17][C:14]43[CH3:15])[C:1]1([CH3:29]) [CH3:27] [H:69][CH:26]([H:70])[C:5](=[CH:6][CH2:7][CH2:8][C:9](=[CH:10][CH2:11] [CH2:12][CH:13]=[C:14]([CH3:15])[CH2:16][CH2:17][CH:19]=[C:20]([CH3:21]) (3S)-2,3-epoxy-2,3- [CH:23]([H:48])[CH2:25][CH:27]1[O:22][C:29]1([CH3:18])[CH3:31])[CH3:24]) dihydrosqualene [CH2:4][CH2:3][CH:2]=[C:1]([CH3:28])[CH3:30]>>[H:48][O:22] 5.4.99.38 mutase (cyclizing, [CH:26]1[CH2:25][CH:23]=[C:20]([CH3:21])[CH:19]([CH2:17][CH2:16][C:14] camelliol-C- (=[CH:13][CH2:12][CH2:11][CH:10]=[C:9]([CH3:24])[CH2:8][CH2:7] forming) [CH:6]=[C:5]([CH:27]([H:70])[H:69])[CH2:4][CH2:3][CH:2]=[C:1]([CH3:30]) [CH3:28])[CH3:15])[C:29]1([CH3:31])[CH3:18] [H:67][C:6](=[C:5]([CH3:26])[CH2:4][C:3]([H:73])([H:74])[CH:2]=[C:1] ([CH3:28])[CH3:30])[CH2:7][CH2:8][C:9](=[C:10]([H:59])[CH:11]([H:58]) (3S)-2,3-epoxy-2,3- [CH2:12][CH:13]=[C:14]([CH3:15])[CH2:16][CH2:17][CH:19]=[C:20]([CH3:21]) dihydrosqualene [CH2:23][CH2:25][CH:27]1[O:22][C:29]1([CH3:18])[CH3:31])[CH3:24]>>[H:73] 5.4.99.39 mutase (cyclizing, [O:22][CH:27]1[CH2:25][CH2:23][C:20]2([CH3:21])[CH:19]([CH2:17][CH2:16] beta-amyrin- [C:14]3([CH3:15])[CH:13]2[CH2:12][CH:11]=[C:10]4[C:5]5([H:74])[CH2:4][C:3] forming) ([CH3:30])([CH3:28])[CH:2]([H:67])[C:1]([H:59])([H:58])[C:6]5([CH3:26]) [CH2:7][CH2:8][C:9]43[CH3:24])[C:29]1([CH3:18])[CH3:31] [H:67][C:6](=[C:5]([CH3:26])[CH2:4][CH:3]([H:74])[CH:2]=[C:1]([CH3:30]) [CH:28]([H:77])[H:78])[CH2:7][CH2:8][C:9](=[C:10]([H:59])[CH:11]([H:58]) (3S)-2,3-epoxy-2,3- [CH2:12][CH:13]=[C:14]([CH3:15])[CH2:16][CH2:17][CH:19]=[C:20]([CH3:21]) dihydrosqualene [CH2:23][CH2:25][CH:27]1[O:22][C:29]1([CH3:18])[CH3:31])[CH3:24]>>[H:77] 5.4.99.40 mutase (cyclizing, [O:22][CH:27]1[CH2:25][CH2:23][C:20]2([CH3:21])[CH:19]([CH2:17][CH2:16] alpha-amyrin- [C:14]3([CH3:15])[CH:13]2[CH2:12][CH:11]=[C:10]4[CH:28]5[CH:2]([C:1] forming) ([H:67])([H:74])[H:78])[CH:3]([CH3:30])[CH2:4][C:5]([H:59])([H:58]) [C:6]5([CH3:26])[CH2:7][CH2:8][C:9]43[CH3:24])[C:29]1([CH3:18])[CH3:31] [H:75][C:2](=[C:1]([CH3:28])[CH2:30][H:81])[CH2:3][CH2:4][C:5](=[CH:6] [CH2:7][CH:8]([H:64])[C:9](=[CH:10][CH2:11][CH2:12][CH:13]=[C:14] ([CH3:15])[CH2:16][CH2:17][CH:19]=[C:20]([CH3:21])[CH2:23][CH2:25] (3S)-2,3-epoxy-2,3- [CH:27]1[O:22][C:29]1([CH3:18])[CH3:31])[C:24]([H:60])([H:61])[H:62]) dihydrosqualene 5.4.99.41 [CH3:26]>>[H:75][O:22][CH:27]1[CH2:25][CH2:23][C:20]2([CH3:21])[CH:19] mutase (cyclizing, ([CH2:17][CH2:16][C:14]3([CH3:15])[CH:13]2[CH2:12][CH2:11] lupeol-forming) [CH:10]4[C:9]5([H:81])[CH:8]([C:24](=[CH2:30])[CH3:28])[CH2:7][CH:6] ([H:64])[C:5]5([CH3:26])[CH2:4][CH2:3][C:2]43[C:1]([H:62])([H:60])[H:61]) [C:29]1([CH3:18])[CH3:31] 5.4.99.46 (3S)-2,3-epoxy-2,3- [H:55][C:12]([H:56])([CH:13]=[C:14]([CH3:15])[CH2:16][C:17]([H:50])([H:51]) dihydrosqualene [CH:19]=[C:20]([CH3:21])[CH2:23][CH2:25][CH:27]1[O:22][C:29]1([CH3:18]) mutase (cyclizing, [CH3:31])[CH2:11][CH:10]=[C:9]([CH3:24])[C:8]([H:63])([H:64])[CH2:7] shionone-forming) [CH:6]=[C:5]([CH3:26])[CH2:4][CH2:3][CH:2]=[C:1]([CH3:28])

40 [CH3:30]>>[H:63][CH:6]1[CH2:7][C:8]2([CH3:15])[CH:27]3[CH2:25][CH2:23] [C:20]4([CH3:21])[CH:19]([C:17](=[O:22])[CH2:16][C:14]([H:64])([H:55]) [CH:13]4[C:12]3([CH3:31])[CH2:11][CH:10]([H:56])[C:9]2([CH3:24])[C:29] ([H:50])([H:51])[C:5]1([CH3:26])[CH2:4][CH2:3][CH:2]=[C:1]([CH3:30]) [CH3:28])[CH3:18] [H:59][C:10](=[C:9]([CH3:24])[CH2:8][CH2:7][CH:6]=[C:5]([CH3:26])[CH2:4] [CH2:3][CH:2]=[C:1]([CH3:28])[CH3:30])[CH2:11][CH:12]([H:56])[C:13] (3S)-2,3-epoxy-2,3- ([H:54])=[C:14]([CH3:15])[CH2:16][CH2:17][CH:19]=[C:20]([CH3:21])[CH2:23] dihydrosqualene [CH2:25][CH:27]1[O:22][C:29]1([CH3:18])[CH3:31]>>[H:59][O:22] 5.4.99.47 mutase (cyclizing, [CH:27]1[CH2:25][CH2:23][C:20]2([C:13]3=[CH:12][CH2:11][C:10]4([CH3:15]) parkeol-forming) [CH:6]([CH2:7][CH2:8][C:9]4([CH3:24])[C:14]3([H:56])[CH2:16][CH2:17] [CH:19]2[C:29]1([CH3:18])[CH3:31])[C:5]([H:54])([CH3:26])[CH2:4][CH2:3] [CH:2]=[C:1]([CH3:30])[CH3:28])[CH3:21] [H:59][C:10](=[C:9]([CH3:24])[CH2:8][CH2:7][C:6]([H:67])=[C:5]([CH3:26]) [CH2:4][C:3]([H:73])([H:74])[CH:2]=[C:1]([CH3:28])[CH3:30])[CH2:11][CH2:12] (3S)-2,3-epoxy-2,3- [CH:13]=[C:14]([CH3:15])[CH2:16][CH2:17][CH:19]=[C:20]([CH2:21][H:44]) dihydrosqualene [CH2:23][CH2:25][CH:27]1[O:22][C:29]1([CH3:18])[CH3:31]>>[H:73][O:22] 5.4.99.48 mutase (cyclizing, [CH:27]1[CH2:25][CH2:23][C:20](=[CH2:21])[CH:19]([CH2:17][CH2:16][C:14] achilleol-B- (=[CH:13][CH2:12][CH2:11][C:10]2=[C:9]([CH3:24])[CH2:8][CH2:7] forming) [C:6]3([CH3:28])[C:1]([H:74])([H:67])[CH:2]([H:59])[C:3]([CH3:30])([CH3:26]) [CH2:4][C:5]23[H:44])[CH3:15])[C:29]1([CH3:18])[CH3:31] [H:49][C:19](=[C:20]([C:21]([H:40])([H:41])[H:44])[CH2:23][CH2:25] [CH:27]1[O:22][C:29]1([CH3:18])[CH3:31])[CH2:17][CH2:16][C:14](=[CH:13] [CH2:12][C:11]([H:57])([H:58])[CH:10]=[C:9]([CH3:24])[C:8]([H:63])([H:64]) (3S)-2,3-epoxy-2,3- [CH2:7][CH:6]=[C:5]([CH3:26])[CH:4]([H:72])[CH2:3][CH:2]=[C:1]([CH3:28]) dihydrosqualene 5.4.99.49 [CH3:30])[CH3:15]>>[H:72][O:22][CH:27]1[CH2:25][CH2:23][C:20]2([H:63]) mutase (cyclizing, [C:21](=[CH:2][CH2:3][CH:4]3[C:19]2([CH3:24])[CH2:17][CH2:16] glutinol-forming) [C:14]4([CH3:15])[CH:13]5[CH2:12][C:11]([CH3:30])([CH3:28])[CH:10]([H:64]) [C:9]([H:58])([H:57])[C:8]5([C:1]([H:49])([H:40])[H:41])[CH2:7][CH:6]([H:44]) [C:5]34[CH3:26])[C:29]1([CH3:31])[CH3:18] [H:75][C:2](=[C:1]([CH3:28])[CH3:30])[CH2:3][CH2:4][C:5](=[C:6]([H:67]) [CH2:7][CH2:8][C:9](=[CH:10][CH2:11][C:12]([H:55])([H:56])[CH:13]=[C:14] ([CH3:15])[C:16]([H:52])([H:53])[CH2:17][CH:19]=[C:20]([CH3:21])[CH:23] (3S)-2,3-epoxy-2,3- ([H:48])[CH2:25][CH:27]1[O:22][C:29]1([CH3:18])[CH3:31])[CH3:24]) dihydrosqualene 5.4.99.50 [CH3:26]>>[H:55][CH:27]1[CH2:25][CH:23]2[C:6]([CH3:30])([CH2:7][CH2:8] mutase (cyclizing, [C:9]3([CH3:24])[CH:10]4[CH2:11][C:12]([CH3:18])([CH3:15])[CH:13]([H:56]) friedelin-forming) [C:14]([H:53])([H:52])[C:16]4([CH3:26])[CH2:17][CH:19]([H:48]) [C:20]23[CH3:21])[C:5]5([H:67])[CH2:4][CH2:3][C:2](=[O:22])[C:1]([H:75]) ([CH3:28])[C:29]15[CH3:31] [H:49][C:19](=[C:20]([CH3:21])[CH2:23][CH2:25][C:27]1([H:43])[O:22] [C:29]1([CH3:31])[CH2:18][H:42])[CH:17]([H:51])[CH2:16][C:14](=[CH:13] (3S)-2,3-epoxy-2,3- [C:12]([H:55])([H:56])[CH2:11][CH:10]=[C:9]([CH3:24])[C:8]([H:63])([H:64]) dihydrosqualene [CH2:7][CH:6]=[C:5]([CH3:26])[CH2:4][CH2:3][CH:2]=[C:1]([CH3:28]) 5.4.99.51 mutase (cyclizing, [CH3:30])[CH3:15]>>[H:51][C:29]([H:49])([H:56])[C:19]1([CH3:21]) baccharis-oxide- [C:20]2([H:43])[O:22][C:27]3([CH2:25][CH2:23]2)[CH:17]1[CH2:16][C:14] forming) ([H:55])([H:64])[CH:13]4[C:8]5([CH3:15])[CH2:7][CH:6]([H:63])[C:5]([CH3:26]) ([CH2:4][CH2:3][CH:2]=[C:1]([CH3:30])[CH3:28])[CH2:18][C:9]5([CH3:24]) [CH:10]([H:42])[CH2:11][C:12]43[CH3:31] [H:59][C:10](=[C:9]([CH3:24])[CH2:8][CH2:7][C:6]([H:67])=[C:5]([CH:26] ([H:69])[H:70])[CH2:4][CH:3]([H:74])[CH:2]=[C:1]([CH3:28])[CH3:30])[CH2:11] (3S)-2,3-epoxy-2,3- [CH2:12][CH:13]=[C:14]([CH3:15])[CH:16]([H:53])[CH2:17][CH:19]=[C:20] dihydrosqualene ([CH3:21])[CH2:23][CH2:25][CH:27]1[O:22][C:29]1([CH3:18])[CH3:31]>>[H:74] 5.4.99.52 mutase (cyclizing, [O:22][CH:27]1[CH2:25][CH2:23][C:20]2([CH3:21])[CH:13]([C:14](=[CH:16] alpha-seco-amyrin- [CH2:17][CH:19]2[C:29]1([CH3:31])[CH3:18])[CH3:15])[CH2:12][CH2:11] forming) [C:10]3=[C:9]([CH3:24])[CH2:8][CH2:7][C:6]4([CH3:28])[C:5]([H:59])([H:67]) [CH2:4][CH:3]([CH3:30])[CH:2]([C:1]([H:53])([H:70])[H:69])[CH:26]34 5.4.99.53 (3S)-2,3-epoxy-2,3- [H:39][CH:18]([H:42])[C:29]1([O:22][CH:27]1[CH2:25][CH2:23][C:20](=[CH:19] dihydrosqualene [CH2:17][CH2:16][C:14](=[CH:13][CH2:12][CH2:11][CH:10]=[C:9]([CH3:24]) mutase (cyclizing, [CH2:8][CH2:7][CH:6]=[C:5]([CH3:26])[CH2:4][CH2:3][CH:2]=[C:1]([CH3:28])

41 [CH3:30])[CH3:15])[CH3:21])[CH3:31]>>[H:39][CH:13]([H:42])[C:14] (=[C:20]1[CH2:23][CH2:25][CH:27]([CH3:21])[C:29]([CH3:31])([CH2:12] marneral-forming) [CH2:11][CH:10]=[C:9]([CH3:24])[CH2:8][CH2:7][CH:6]=[C:5]([CH3:26]) [CH2:4][CH2:3][CH:2]=[C:1]([CH3:28])[CH3:30])[CH:18]1[CH2:16][CH2:17] [CH:19]=[O:22])[CH3:15] [H:59][C:10](=[C:9]([CH3:24])[CH2:8][CH2:7][C:6]([H:67])=[C:5]([CH3:26]) [CH2:4][C:3]([H:73])([H:74])[CH:2]=[C:1]([CH3:28])[CH3:30])[CH2:11][CH2:12] (3S)-2,3-epoxy-2,3- [CH:13]=[C:14]([CH3:15])[CH:16]([H:53])[CH2:17][CH:19]=[C:20]([CH3:21]) dihydrosqualene [CH2:23][CH2:25][CH:27]1[O:22][C:29]1([CH3:18])[CH3:31]>>[H:73][O:22] 5.4.99.54 mutase (cyclizing, [CH:27]1[CH2:25][CH2:23][C:20]2([CH3:21])[CH:13]([C:14](=[CH:16][CH2:17] beta-seco-amyrin- [CH:19]2[C:29]1([CH3:31])[CH3:18])[CH3:15])[CH2:12][CH2:11][C:10]3=[C:9] forming) ([CH3:24])[CH2:8][CH2:7][C:6]4([CH3:28])[C:5]([H:67])([H:74])[CH2:4][C:3] ([CH3:26])([CH3:30])[CH:2]([H:59])[C:1]34[H:53] [H:59][C:10](=[C:9]([CH3:24])[CH2:8][C:7]([H:65])([H:66])[CH:6]=[C:5] ([CH3:26])[C:4]([H:71])([H:72])[CH2:3][CH:2]=[C:1]([CH3:28])[CH3:30]) (3S)-2,3-epoxy-2,3- [CH2:11][CH2:12][CH:13]=[C:14]([CH3:15])[CH2:16][CH2:17][CH:19]=[C:20] dihydrosqualene ([CH3:21])[CH2:23][CH2:25][CH:27]1[O:22][C:29]1([CH3:18])[CH3:31]>>[H:71] 5.4.99.55 mutase (cyclizing, [O:22][CH:27]1[CH2:25][CH2:23][C:20]2([CH3:21])[CH:19]([CH2:17][CH2:16] delta-amyrin- [C:14]3([CH3:15])[CH:13]2[CH2:12][CH2:11][C:10]4=[C:9]5[CH2:8][C:7] forming) ([CH3:24])([CH3:30])[CH:6]([H:72])[C:5]([H:66])([H:65])[C:4]5([CH3:26]) [CH2:3][CH:2]([H:59])[C:1]43[CH3:28])[C:29]1([CH3:31])[CH3:18] [H:59][C:10](=[C:9]([CH3:24])[CH2:8][CH2:7][CH:6]=[C:5]([CH3:26])[CH2:4] [CH2:3][CH:2]=[C:1]([CH3:28])[CH3:30])[CH2:11][CH2:12][CH:13]=[C:14] (3S)-2,3-epoxy-2,3- ([CH3:15])[CH:16]([H:53])[CH2:17][CH:19]=[C:20]([CH3:21])[CH2:23][CH2:25] dihydrosqualene [CH:27]1[O:22][C:29]1([CH3:18])[CH3:31]>>[H:59][O:22][CH:27]1[CH2:25] 5.4.99.56 mutase (cyclizing, [CH2:23][C:20]2([CH3:21])[CH:13]3[C:14](=[CH:16][CH2:17] tirucalla-7,24-dien- [CH:19]2[C:29]1([CH3:18])[CH3:31])[C:9]4([CH3:24])[CH2:8][CH2:7][CH:6] 3beta-ol-forming) ([C:5]([H:53])([CH3:26])[CH2:4][CH2:3][CH:2]=[C:1]([CH3:30])[CH3:28]) [C:10]4([CH3:15])[CH2:11][CH2:12]3 [H:75][C:2](=[C:1]([CH3:28])[CH2:30][H:81])[CH:3]([H:74])[CH2:4][C:5] (=[CH:6][C:7]([H:65])([H:66])[CH:8]([H:64])[C:9](=[CH:10][C:11]([H:57]) ([H:58])[CH2:12][CH:13]=[C:14]([CH3:15])[C:16]([H:52])([H:53])[CH2:17] (3S)-2,3-epoxy-2,3- [CH:19]=[C:20]([CH3:21])[CH2:23][CH2:25][CH:27]1[O:22][C:29]1([CH3:18]) dihydrosqualene 5.4.99.57 [CH3:31])[CH3:24])[CH3:26]>>[H:75][O:22][CH:3]1[CH2:4][C:5]([H:74])([H:81]) mutase (cyclizing, [CH:6]2[C:7](=[CH:8][C:9]([H:65])([H:66])[CH:10]3[C:11]2([CH3:28])[CH2:12] baruol-forming) [CH:13]([H:64])[C:14]4([CH3:15])[CH2:30][C:20]([CH3:21])([CH2:23][CH2:25] [CH:27]=[C:29]([CH3:31])[CH3:18])[CH:19]([H:57])[CH2:17][C:16]34[CH3:24]) [C:2]1([CH3:26])[C:1]([H:58])([H:52])[H:53] [H:20][CH:5]([CH2:6][CH2:7][CH2:9][NH2:8])[CH:1]([NH2:10])[C:2](=[O:3]) L-lysine carboxy- 5.4.99.58 [OH:4]>>[H:20][CH2:9][CH:5]([CH2:6][CH2:7][NH2:8])[CH:1]([NH2:10])[C:2] aminomethylmutase (=[O:3])[OH:4] [H:54][O:28][CH:13]1[CH:9]([O:30][CH:32]([CH:33]([H:58])[H:59])[CH:16] ([OH:17])[CH:15]1[O:23][H:50])[O:8][P:35](=[O:5])([OH:7])[O:34][P:27] (=[O:29])([OH:31])[O:26][CH:25]([H:52])[CH:21]2[O:24][CH:18]([n:11]3[cH:1] dTDP-alpha-D- [c:2]([c:3](=[O:6])[nH:4][c:12]3=[O:14])[CH3:10])[CH:19]([H:48]) 5.4.99.59 fucopyranose [CH:20]2[OH:22]>>[H:48][O:26][CH:25]([CH:9]([H:52])[H:58])[CH:21]1[O:24] furanomutase [CH:18]([O:8][P:35](=[O:5])([OH:7])[O:34][P:27](=[O:29])([OH:31])[O:28] [CH:13]([H:59])[CH:15]2[O:23][CH:33]([n:11]3[cH:1][c:2]([c:3](=[O:6])[nH:4] [c:12]3=[O:14])[CH3:10])[CH:32]([H:50])[CH:16]2[OH:17])[CH:19]([O:30] [H:54])[CH:20]1[OH:22] 5.4.99.60 precorrin-8 11,12- [H:110][CH:3]1[C:2]=2[N:51]=[C:52]([C:20](=[C:21]3[N:49]([Co+:63])[C:48] methylmutase ([CH3:50])([CH:53]4[N:46]=[C:31]([C:29]([H:105])([C:18]5=[N:28][C:4]1([C:5] (=[C:6]5[CH2:7][CH2:8][C:9](=[O:10])[OH:11])[CH3:19])[CH3:22])[CH3:47]) [C:32]([CH3:33])([CH2:34][CH2:37][C:38](=[O:42])[OH:43])[CH:45]4[CH2:54] [C:55](=[O:57])[OH:60])[C:35]([CH3:36])([CH2:39][C:40](=[O:41])[OH:44]) [CH:23]3[CH2:24][CH2:25][C:26](=[O:27])[OH:30])[CH3:64])[C:12] ([C:1]2[CH2:56][CH2:58][C:59](=[O:61])[OH:62])([CH3:13])[CH2:14][C:15] (=[O:16])[OH:17]>>[H:110][C:1]1([C:2]=2[N:51]=[C:52]([C:20](=[C:21]3[N:49] ([Co+:63])[C:48]([CH3:50])([CH:53]4[N:46]=[C:31]([C:29](=[C:18]5[N:28]=[C:4]

42 ([CH:3]2)[C:5]([CH3:22])([CH3:19])[C:6]5([H:105])[CH2:7][CH2:8][C:9] (=[O:10])[OH:11])[CH3:47])[C:32]([CH3:33])([CH2:34][CH2:37][C:38](=[O:42]) [OH:43])[CH:45]4[CH2:54][C:55](=[O:57])[OH:60])[C:35]([CH3:36])([CH2:39] [C:40](=[O:41])[OH:44])[CH:23]3[CH2:24][CH2:25][C:26](=[O:27])[OH:30]) [CH3:64])[C:12]1([CH3:13])[CH2:14][C:15](=[O:16])[OH:17])[CH2:56][CH2:58] [C:59](=[O:61])[OH:62] [H:123][CH:35]1[C:31]2=[N:34][C:1](=[C:2]([C:3]3=[N:29][C:28]([CH3:30]) ([CH:32]4[N:59]=[C:55]([C:62]([H:121])([C:56]5=[N:60][C:36]1([C:39] (=[C:40]5[CH2:41][CH2:44][C:45](=[O:46])[OH:49])[CH3:57])[CH3:58]) [CH3:61])[C:47]([CH3:48])([CH2:50][CH2:51][C:52](=[O:53])[OH:54]) [CH:33]4[CH2:37][C:38](=[O:42])[OH:43])[C:12]([CH3:16])([CH2:18][C:19] (=[O:20])[OH:21])[CH:4]3[CH2:5][CH2:6][C:7](=[O:8])[OH:9])[CH3:63])[C:10] ([CH3:11])([CH2:13][C:14](=[O:15])[OH:17])[CH:22]2[CH2:23][CH2:24][C:25] precorrin 8X 11,12- 5.4.99.61 (=[O:26])[OH:27]>>[H:123][N:59]1[C:55]2=[C:62]([C:56]3=[N:60][C:36] methylmutase (=[CH:35][C:31]4=[N:34][C:1](=[C:2]([C:3]5=[N:29][C:28]([CH3:30]) ([CH:32]1[CH:33]([CH2:37][C:38](=[O:42])[OH:43])[C:47]2([CH3:48])[CH2:50] [CH2:51][C:52](=[O:53])[OH:54])[C:12]([CH3:16])([CH2:18][C:19](=[O:20]) [OH:21])[CH:4]5[CH2:5][CH2:6][C:7](=[O:8])[OH:9])[CH3:63])[C:10]([CH3:11]) ([CH2:13][C:14](=[O:15])[OH:17])[CH:22]4[CH2:23][CH2:24][C:25](=[O:26]) [OH:27])[C:39]([CH3:58])([CH3:57])[C:40]3([H:121])[CH2:41][CH2:44][C:45] (=[O:46])[OH:49])[CH3:61] 2,5-Dihydro-5- [H:14][CH:8]([C:9](=[O:10])[OH:6])[CH:7]1[O:5][C:3](=[O:4]) 5.5.1.1 oxofuran-2-acetate [CH:2]=[CH:1]1>>[H:14][O:5][C:3](=[O:4])[CH:2]=[CH:1][CH:7]=[CH:8][C:9] lyase (decyclizing) (=[O:10])[OH:6] 2-Carboxy-2,5- [H:18][CH:12]([C:13](=[O:6])[OH:10])[C:7]1([O:5][C:3](=[O:4])[CH:2]=[CH:1]1) dihydro-5-oxofuran- 5.5.1.2 [C:8](=[O:9])[OH:11]>>[H:18][O:5][C:3](=[O:4])[CH:2]=[CH:1][C:7](=[CH:12] 2-acetate lyase [C:13](=[O:6])[OH:10])[C:8](=[O:9])[OH:11] (decyclizing) Tetrahydroxypteridi [H:17][O:14][c:13]1[n:4][c:3]([O:5][H:15])[c:2]2[n:7][c:8]([OH:10])[c:9]([O:12] 5.5.1.3 ne lyase [H:18])[n:6][c:1]2[n:11]1>>[H:15][n:4]1[c:13](=[O:14])[n:11]([H:17])[c:1]2[n:6] (isomerizing) [c:9]([n:7]([H:18])[c:2]2[c:3]1=[O:5])[C:8](=[O:12])[OH:10] [H:17][CH:15]([O:5][P:6](=[O:8])([OH:9])[OH:11])[CH:13]1[O:14][CH:4]([OH:7]) 1D-myo-inositol-3- [CH:3]([OH:10])[CH:2]([OH:12])[CH:1]1[OH:16]>>[H:17][O:14][CH:15]1[CH:4] 5.5.1.4 phosphate lyase ([OH:7])[CH:3]([OH:10])[CH:2]([OH:12])[CH:1]([OH:16])[CH:13]1[O:5][P:6] (isomerizing) (=[O:8])([OH:9])[OH:11] 3-carboxy-2,5- [H:15][O:10][C:7](=[O:8])[C:1]1=[CH:2][C:3](=[O:4])[O:5][CH:11]1[CH:12] dihydro-5-oxofuran- 5.5.1.5 ([H:18])[C:13](=[O:6])[OH:9]>>[H:15][O:5][C:3](=[O:4])[CH:2]=[C:1] 2-acetate lyase ([CH:11]=[CH:12][C:13](=[O:6])[OH:9])[C:7](=[O:10])[O:8][H:18] (decyclizing) 2-Chloro-2,5- [H:15][CH:7]([C:8](=[O:9])[OH:11])[C:6]1([Cl:10])[O:5][C:3](=[O:4]) dihydro-5-oxofuran- 5.5.1.7 [CH:2]=[CH:1]1>>[H:15][O:5][C:3](=[O:4])[CH:2]=[CH:1][C:6]([Cl:10])=[CH:7] 2-acetate lyase [C:8](=[O:9])[OH:11] (decyclizing) [H:27][CH:7]1[CH:8]([O:9][P:10](=[O:11])([OH:13])[O:15][P:17](=[O:19]) (+)-Bornyl- ([OH:5])[OH:6])[C:4]2([CH3:18])[CH2:3][CH2:2][C:1]1([H:39]) 5.5.1.8 diphosphate lyase [C:12]2([CH3:14])[CH3:16]>>[H:39][C:4](=[C:12]([CH3:14])[CH3:16])[CH2:3] (decyclizing) [CH2:2][C:1](=[CH:7][CH:8]([H:27])[O:9][P:10](=[O:11])([OH:13])[O:15][P:17] (=[O:19])([OH:5])[OH:6])[CH3:18] [H:65][C:21]12[CH2:22][CH2:23][CH:12]3[CH:13]([CH3:15])[CH:7]([OH:8]) [CH2:31][CH2:29][C:26]43[CH2:25][C:24]24[CH2:19][CH2:18][C:16]5([CH3:17]) Cycloeucalenol [CH:9]([CH2:10][CH2:11][C:14]15[CH3:20])[CH:5]([CH3:6])[CH2:4][CH2:3] lyase [C:2](=[CH2:1])[CH:27]([CH3:28])[CH3:30]>>[H:65][CH2:25] 5.5.1.9 (cyclopropane- [C:26]12[C:24]3=[C:21]([CH2:22][CH2:23][CH:12]2[CH:13]([CH3:15])[CH:7] decyclizing) ([OH:8])[CH2:31][CH2:29]1)[C:14]4([CH3:20])[CH2:11][CH2:10][CH:9]([CH:5] ([CH3:6])[CH2:4][CH2:3][C:2](=[CH2:1])[CH:27]([CH3:28])[CH3:30]) [C:16]4([CH3:17])[CH2:18][CH2:19]3 5.5.1.10 alpha-Pinene-oxide [H:18][C:3]12[CH2:4][CH:5]3[O:6][C:9]3([CH3:11])[CH:1]([CH2:2]1) lyase (decyclizing) [C:7]2([CH3:8])[CH3:10]>>[H:18][C:7]([C:3](=[CH2:4])[CH2:2][CH:1]=[C:9]

43 ([CH:5]=[O:6])[CH3:11])([CH3:10])[CH3:8] 2,4-Dichloro-2,5- [H:14][CH:8]([C:9](=[O:10])[OH:11])[C:7]1([Cl:12])[O:5][C:3](=[O:4])[C:2] dihydro-5-oxofuran- 5.5.1.11 ([Cl:6])=[CH:1]1>>[H:14][O:5][C:3](=[O:4])[C:2]([Cl:6])=[CH:1][C:7] 2-acetate lyase ([Cl:12])=[CH:8][C:9](=[O:10])[OH:11] (decyclizing) [H:44][CH2:24][C:9](=[CH:10][CH2:11][CH2:12][C:13](=[CH:14][CH2:15][O:17] [P:18](=[O:19])([OH:20])[O:21][P:22](=[O:23])([OH:25])[OH:28])[CH3:16]) (+)-copalyl- [CH2:8][CH2:7][CH:6]=[C:5]([CH3:26])[CH2:4][CH2:3][CH:2]=[C:1]([CH3:27]) 5.5.1.12 diphosphate lyase [CH3:29]>>[H:44][CH:2]1[CH2:3][CH2:4][C:5]2([CH3:26])[CH:10]([C:9] (decyclizing) (=[CH2:24])[CH2:8][CH2:7][CH:6]2[C:1]1([CH3:29])[CH3:27])[CH2:11][CH2:12] [C:13](=[CH:14][CH2:15][O:17][P:18](=[O:19])([OH:20])[O:21][P:22](=[O:23]) ([OH:25])[OH:28])[CH3:16] [H:44][CH2:24][C:9](=[CH:10][CH2:11][CH2:12][C:13](=[CH:14][CH2:15][O:17] [P:18](=[O:19])([OH:20])[O:21][P:22](=[O:23])([OH:25])[OH:28])[CH3:16]) [CH2:8][CH2:7][CH:6]=[C:5]([CH3:26])[CH2:4][CH2:3][CH:2]=[C:1]([CH3:27]) ent-Copalyl- 5.5.1.13 [CH3:29]>>[H:44][CH:2]1[CH2:3][CH2:4][C:5]2([CH3:26])[CH:10]([C:9] diphosphate lyase (=[CH2:24])[CH2:8][CH2:7][CH:6]2[C:1]1([CH3:29])[CH3:27])[CH2:11][CH2:12] [C:13](=[CH:14][CH2:15][O:17][P:18](=[O:19])([OH:20])[O:21][P:22](=[O:23]) ([OH:25])[OH:28])[CH3:16] [H:44][CH2:24][C:9](=[CH:10][CH2:11][CH2:12][C:13](=[CH:14][CH2:15][O:17] [P:18](=[O:19])([OH:20])[O:21][P:22](=[O:23])([OH:25])[OH:28])[CH3:16]) 9alpha-Copalyl- [CH2:8][CH2:7][CH:6]=[C:5]([CH3:26])[CH2:4][CH2:3][CH:2]=[C:1]([CH3:27]) 5.5.1.14 diphosphate lyase [CH3:29]>>[H:44][CH:2]1[CH2:3][CH2:4][C:5]2([CH3:26])[CH:10]([C:9] (decyclizing) (=[CH2:24])[CH2:8][CH2:7][CH:6]2[C:1]1([CH3:29])[CH3:27])[CH2:11][CH2:12] [C:13](=[CH:14][CH2:15][O:17][P:18](=[O:19])([OH:20])[O:21][P:22](=[O:23]) ([OH:25])[OH:28])[CH3:16] [H:49][C:6](=[C:5]([CH3:26])[CH2:4][CH2:3][CH:2]=[C:1]([CH3:27])[CH3:29]) [CH2:7][CH2:8][C:9](=[C:10]([H:41])[CH2:11][CH2:12][C:13](=[CH:14][CH2:15] terpentedienyl- [O:17][P:18](=[O:19])([OH:20])[O:21][P:22](=[O:23])([OH:25])[OH:28]) 5.5.1.15 diphosphate lyase [CH3:16])[CH3:24]>>[H:41][C:9]1([CH3:24])[CH2:8][CH2:7][C:6]2([C:1] (decyclizing) (=[CH:2][CH2:3][CH2:4][C:5]2([H:49])[C:10]1([CH3:26])[CH2:11][CH2:12] [C:13](=[CH:14][CH2:15][O:17][P:18](=[O:19])([OH:20])[O:21][P:22](=[O:23]) ([OH:28])[OH:25])[CH3:16])[CH3:27])[CH3:29] [H:41][C:10](=[C:9]([CH3:24])[CH2:8][CH:7]([H:48])[C:6]([H:49])=[C:5] ([CH3:26])[CH2:4][CH2:3][CH:2]=[C:1]([CH3:27])[CH3:29])[CH2:11][CH2:12] halima-5(6),13- [C:13](=[CH:14][CH2:15][O:17][P:18](=[O:19])([OH:20])[O:21][P:22](=[O:23]) dien-15-yl- 5.5.1.16 ([OH:25])[OH:28])[CH3:16]>>[H:49][CH:2]1[CH2:3][CH2:4][C:5]2([H:41])[C:6] diphosphate lyase (=[CH:7][CH2:8][C:9]([H:48])([CH3:24])[C:10]2([CH3:26])[CH2:11][CH2:12] (cyclizing) [C:13](=[CH:14][CH2:15][O:17][P:18](=[O:19])([OH:20])[O:21][P:22](=[O:23]) ([OH:28])[OH:25])[CH3:16])[C:1]1([CH3:27])[CH3:29] [H:43][CH:24]([C:22](=[CH:21][CH:20]=[CH:19][C:18](=[CH:17] [CH:16]=[CH:15][C:14](=[CH:13][CH:12]=[CH:11][CH:10]=[C:9]([CH:8]=[CH:7] [CH:6]=[C:5]([CH:4]=[CH:3][CH:2]=[C:1]([CH3:33])[CH2:34][CH2:35] [CH:36]=[C:37]([CH3:38])[CH3:40])[CH3:32])[CH3:30])[CH3:28])[CH3:27]) carotenoid psi-end [CH3:23])[CH2:25][CH:26]=[C:29]([CH3:31])[CH3:39]>>[H:43] 5.5.1.18 group lyase [CH:26]1[CH2:25][CH:24]=[C:22]([CH3:23])[CH:21]([CH:20]=[CH:19][C:18] (decyclizing) (=[CH:17][CH:16]=[CH:15][C:14](=[CH:13][CH:12]=[CH:11][CH:10]=[C:9] ([CH:8]=[CH:7][CH:6]=[C:5]([CH:4]=[CH:3][CH:2]=[C:1]([CH3:33])[CH2:34] [CH2:35][CH:36]=[C:37]([CH3:38])[CH3:40])[CH3:32])[CH3:30])[CH3:28]) [CH3:27])[C:29]1([CH3:31])[CH3:39] 5.5.1.19 carotenoid beta-end [H:80][C:2]([CH:3]=[CH:4][C:5](=[CH:6][CH:7]=[CH:8][C:9](=[CH:10] group lyase [CH:11]=[CH:12][CH:13]=[C:14]([CH:15]=[CH:16][CH:17]=[C:18]([CH3:19]) (decyclizing) [CH2:20][CH2:21][CH:22]=[C:23]([CH3:24])[CH2:27][CH2:29][CH:31]=[C:35] ([CH3:38])[CH3:39])[CH3:25])[CH3:26])[CH3:28])=[C:1]([CH3:30])[CH2:32] [CH2:33][CH:34]=[C:36]([CH3:37])[CH3:40]>>[H:80][CH:34]1[CH2:33][CH2:32] [C:1](=[C:2]([CH:3]=[CH:4][C:5](=[CH:6][CH:7]=[CH:8][C:9](=[CH:10] [CH:11]=[CH:12][CH:13]=[C:14]([CH:15]=[CH:16][CH:17]=[C:18]([CH3:19]) [CH2:20][CH2:21][CH:22]=[C:23]([CH3:24])[CH2:27][CH2:29][CH:31]=[C:35] ([CH3:38])[CH3:39])[CH3:25])[CH3:26])[CH3:28])[C:36]1([CH3:40])[CH3:37])

44 [CH3:30] [O:9]=[CH:7][c:6]1[c:18](=[O:19])[o:17][c:3]([CH:2]=[CH:1][CH2:20][CH2:21] [CH2:22][CH2:8][CH:11]=[CH:12][CH:13]=[CH:14][CH3:16])[cH:4][c:5]1[O:10] (-)-solanapyrone-A 5.5.1.20 [CH3:15]>>[O:9]=[CH:7][c:6]1[c:18](=[O:19])[o:17][c:3]([cH:4][c:5]1[O:10] lyase (decyclizing) [CH3:15])[CH:2]2[CH:14]([CH:13]=[CH:12][CH:11]3[CH2:8][CH2:22][CH2:21] [CH2:20][CH:1]32)[CH3:16] [H:32][C:2](=[C:1]([CH3:17])[CH3:19])[CH2:3][CH2:4][C:5](=[CH:6][CH:7] (-)-bornyl- ([H:22])[O:9][P:10](=[O:11])([OH:12])[O:13][P:15](=[O:16])([OH:8])[OH:18]) 5.5.1.22 diphosphate lyase [CH3:14]>>[H:22][CH:6]1[CH:7]([O:9][P:10](=[O:11])([OH:12])[O:13][P:15] (decyclizing) (=[O:16])([OH:8])[OH:18])[C:2]2([CH3:14])[CH2:3][CH2:4][C:5]1([H:32]) [C:1]2([CH3:19])[CH3:17] [H:48][CH:1]([C:2](=[O:3])[O:4][CH3:5])[c:9]1[cH:10][c:11]2[C:12](=[O:21]) [c:13]3[cH:15][cH:16][cH:17][c:19]([OH:20])[c:18]3[C:23](=[O:26])[c:22]2[c:27] aklaviketone lyase ([OH:28])[c:29]1[C:30](=[O:25])[CH2:6][C:7](=[O:24])[CH2:8][CH3:14]>>[H:48] 5.5.1.23 (decyclizing) [O:24][C:7]1([CH2:6][C:30](=[O:25])[c:29]2[c:27]([OH:28])[c:22]3[C:23] (=[O:26])[c:18]4[c:19]([OH:20])[cH:17][cH:16][cH:15][c:13]4[C:12](=[O:21]) [c:11]3[cH:10][c:9]2[CH:1]1[C:2](=[O:3])[O:4][CH3:5])[CH2:8][CH3:14] Benzyl-thiocyanate [N:2]#[C:1][S:3][CH2:4][c:5]1[cH:6][cH:7][cH:8][cH:10] 5.99.1.1 isomerase [cH:9]1>>[S:3]=[C:1]=[N:2][CH2:4][c:5]1[cH:6][cH:7][cH:8][cH:10][cH:9]1 2-hydroxy-2H- chromene-2- carboxylate---(3E)- [H:21][O:14][c:10]1[cH:11][cH:13][cH:12][cH:9][c:8]1[CH:1]=[CH:2][C:3] 5.99.1.4 4-(2- (=[O:7])[C:4](=[O:5])[OH:6]>>[H:21][O:7][C:3]1([O:14][c:10]2[cH:11][cH:13] hydroxyphenyl)-2- [cH:12][cH:9][c:8]2[CH:1]=[CH:2]1)[C:4](=[O:5])[OH:6] oxobut-3-enoate isomerase

45