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Control Engineering Perspective on Genome-Scale Metabolic Modeling
Control Engineering Perspective on Genome-Scale Metabolic Modeling by Andrew Louis Damiani A dissertation submitted to the Graduate Faculty of Auburn University in partial fulfillment of the requirements for the Degree of Doctor of Philosophy Auburn, Alabama December 12, 2015 Key words: Scheffersomyces stipitis, Flux Balance Analysis, Genome-scale metabolic models, System Identification Framework, Model Validation, Phenotype Phase Plane Analysis Copyright 2015 by Andrew Damiani Approved by Jin Wang, Chair, Associate Professor of Chemical Engineering Q. Peter He, Associate Professor of Chemical Engineering, Tuskegee University Thomas W. Jeffries, Professor of Bacteriology, Emeritus; University of Wisconsin-Madison Allan E. David, Assistant Professor of Chemical Engineering Yoon Y. Lee, Professor of Chemical Engineering Abstract Fossil fuels impart major problems on the global economy and have detrimental effects to the environment, which has caused a world-wide initiative of producing renewable fuels. Lignocellulosic bioethanol for renewable energy has recently gained attention, because it can overcome the limitations that first generation biofuels impose. Nonetheless, in order to have this process commercialized, the biological conversion of pentose sugars, mainly xylose, needs to be improved. Scheffersomyces stipitis has a physiology that makes it a valuable candidate for lignocellulosic bioethanol production, and lately has provided genes for designing recombinant Saccharomyces cerevisiae. In this study, a system biology approach was taken to understand the relationship of the genotype to phenotype, whereby genome-scale metabolic models (GSMMs) are used in conjunction with constraint-based modeling. The major restriction of GSMMs is having an accurate methodology for validation and evaluation. This is due to the size and complexity of the models. -
Supplementary Table S1. Table 1. List of Bacterial Strains Used in This Study Suppl
Supplementary Material Supplementary Tables: Supplementary Table S1. Table 1. List of bacterial strains used in this study Supplementary Table S2. List of plasmids used in this study Supplementary Table 3. List of primers used for mutagenesis of P. intermedia Supplementary Table 4. List of primers used for qRT-PCR analysis in P. intermedia Supplementary Table 5. List of the most highly upregulated genes in P. intermedia OxyR mutant Supplementary Table 6. List of the most highly downregulated genes in P. intermedia OxyR mutant Supplementary Table 7. List of the most highly upregulated genes in P. intermedia grown in iron-deplete conditions Supplementary Table 8. List of the most highly downregulated genes in P. intermedia grown in iron-deplete conditions Supplementary Figures: Supplementary Figure 1. Comparison of the genomic loci encoding OxyR in Prevotella species. Supplementary Figure 2. Distribution of SOD and glutathione peroxidase genes within the genus Prevotella. Supplementary Table S1. Bacterial strains Strain Description Source or reference P. intermedia V3147 Wild type OMA14 isolated from the (1) periodontal pocket of a Japanese patient with periodontitis V3203 OMA14 PIOMA14_I_0073(oxyR)::ermF This study E. coli XL-1 Blue Host strain for cloning Stratagene S17-1 RP-4-2-Tc::Mu aph::Tn7 recA, Smr (2) 1 Supplementary Table S2. Plasmids Plasmid Relevant property Source or reference pUC118 Takara pBSSK pNDR-Dual Clonetech pTCB Apr Tcr, E. coli-Bacteroides shuttle vector (3) plasmid pKD954 Contains the Porpyromonas gulae catalase (4) -
Supporting Information
Supporting Information Lee et al. 10.1073/pnas.0903619106 SI Materials and Methods The tobramycin sensitivities for strains expressing the rmtD Plasmids. Plasmid p(amgRSϩ) was constructed by inserting a 2.4 ribosomal methylase gene were determined by a 2-fold broth kb PCR fragment carrying the region from 206 bp upstream of dilution test. Inocula were prepared by growing cells at 37 °C for the amgR start codon to 60 bp downstream of the amgS 16 h in LB lacking NaCl. Cells were diluted to approximately ϫ 6 termination codon into a derivative of pUCP19 (1). Plasmid 3.3 10 cells/ml based on OD600. After a 90 min incubation at 37 °C, 10 l aliquots were distributed to wells (in 96-well format) pRmtD was constructed by inserting the 2.3 kb HindIII-XbaI fragment carrying rmtD from pPA95B1 (2) into a derivative of containing 125 l LB buffered with 0.1 M MOPS at pH 7.6 pUCP19 (1). Plasmids used for complementation studies (Table containing different concentrations of tobramycin. MICs were 1) were constructed in pUCP19 derivatives by inserting PCR determined after incubation for 24 h at 37 °C. fragments corresponding to the genes tested. Plasmid pIbsC was Transcriptional Profiling. MPAO1 and ⌬amgRS transcriptomes constructed by inserting a 1.8 kb PCR fragment carrying the were compared under tobramycin-treated and -untreated con- arabinose-inducible ibsC construct (P -ibsC) from pAZ3-ibsC bad ditions. Samples were prepared in duplicate from independent (3) into a derivative of pUCP19 (4), resulting in pIbsC. The cultures grown in 15 ml LB lacking NaCl. -
Generate Metabolic Map Poster
Authors: Pallavi Subhraveti Anamika Kothari Quang Ong Ron Caspi An online version of this diagram is available at BioCyc.org. Biosynthetic pathways are positioned in the left of the cytoplasm, degradative pathways on the right, and reactions not assigned to any pathway are in the far right of the cytoplasm. Transporters and membrane proteins are shown on the membrane. Ingrid Keseler Peter D Karp Periplasmic (where appropriate) and extracellular reactions and proteins may also be shown. Pathways are colored according to their cellular function. Csac1394711Cyc: Candidatus Saccharibacteria bacterium RAAC3_TM7_1 Cellular Overview Connections between pathways are omitted for legibility. Tim Holland TM7C00001G0420 TM7C00001G0109 TM7C00001G0953 TM7C00001G0666 TM7C00001G0203 TM7C00001G0886 TM7C00001G0113 TM7C00001G0247 TM7C00001G0735 TM7C00001G0001 TM7C00001G0509 TM7C00001G0264 TM7C00001G0176 TM7C00001G0342 TM7C00001G0055 TM7C00001G0120 TM7C00001G0642 TM7C00001G0837 TM7C00001G0101 TM7C00001G0559 TM7C00001G0810 TM7C00001G0656 TM7C00001G0180 TM7C00001G0742 TM7C00001G0128 TM7C00001G0831 TM7C00001G0517 TM7C00001G0238 TM7C00001G0079 TM7C00001G0111 TM7C00001G0961 TM7C00001G0743 TM7C00001G0893 TM7C00001G0630 TM7C00001G0360 TM7C00001G0616 TM7C00001G0162 TM7C00001G0006 TM7C00001G0365 TM7C00001G0596 TM7C00001G0141 TM7C00001G0689 TM7C00001G0273 TM7C00001G0126 TM7C00001G0717 TM7C00001G0110 TM7C00001G0278 TM7C00001G0734 TM7C00001G0444 TM7C00001G0019 TM7C00001G0381 TM7C00001G0874 TM7C00001G0318 TM7C00001G0451 TM7C00001G0306 TM7C00001G0928 TM7C00001G0622 TM7C00001G0150 TM7C00001G0439 TM7C00001G0233 TM7C00001G0462 TM7C00001G0421 TM7C00001G0220 TM7C00001G0276 TM7C00001G0054 TM7C00001G0419 TM7C00001G0252 TM7C00001G0592 TM7C00001G0628 TM7C00001G0200 TM7C00001G0709 TM7C00001G0025 TM7C00001G0846 TM7C00001G0163 TM7C00001G0142 TM7C00001G0895 TM7C00001G0930 Detoxification Carbohydrate Biosynthesis DNA combined with a 2'- di-trans,octa-cis a 2'- Amino Acid Degradation an L-methionyl- TM7C00001G0190 superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis (E. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Metligdb: a Web-Based Database for the Identification of Chemical Groups
computer programs Journal of Applied MetLigDB: a web-based database for the Crystallography identification of chemical groups to design ISSN 0021-8898 metalloprotein inhibitors Received 12 April 2011 Accepted 10 June 2011 Hwanho Choi,‡ Hongsuk Kang‡ and Hwangseo Park* Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-dong, Kwangjin-ku, Seoul 143-747, Korea. Correspondence e-mail: [email protected] MetLigDB (http://silver.sejong.ac.kr/MetLigDB) is a publicly accessible web- based database through which the interactions between a variety of chelating groups and various central metal ions in the active site of metalloproteins can be explored in detail. Additional information can also be retrieved, including protein and inhibitor names, the amino acid residues coordinated to the central metal ion, and the binding affinity of the inhibitor for the target metalloprotein. Although many metalloproteins have been considered promising targets for drug discovery, it is difficult to discover new inhibitors because of the difficulty in designing a suitable chelating moiety to impair the catalytic activity of the central metal ion. Because both common and specific chelating groups can be identified for varying metal ions and the associated coordination environments, # 2011 International Union of Crystallography MetLigDB is expected to give users insight into designing new inhibitors of Printed in Singapore – all rights reserved metalloproteins for drug discovery. 1. Introduction 2008), the coordination geometry around the metal ion (Castagnetto The importance of metal ions in biological systems is increasingly et al., 2002; Andreini, Bertini, Cavallaro, Holliday & Thornton, 2009), drawing attention, as indicated by the recent emergence of terms such catalytic mechanisms (Andreini, Bertini, Cavallaro, Najmanovich & as metallome and metallomics (Shi & Chance, 2008). -
High Coverage Metabolomics Analysis Reveals Phage-Specific Alterations to Pseudomonas Aeruginosa Physiology During Infection
The ISME Journal (2016) 10, 1823–1835 © 2016 International Society for Microbial Ecology All rights reserved 1751-7362/16 www.nature.com/ismej ORIGINAL ARTICLE High coverage metabolomics analysis reveals phage-specific alterations to Pseudomonas aeruginosa physiology during infection Jeroen De Smet1, Michael Zimmermann2, Maria Kogadeeva2, Pieter-Jan Ceyssens1,3, Wesley Vermaelen1, Bob Blasdel1, Ho Bin Jang1, Uwe Sauer2 and Rob Lavigne1 1Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Heverlee, Belgium; 2Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zürich, Zürich, Switzerland and 3Unit Bacterial Diseases, Scientific Institute of Public Health (WIV-ISP), Brussels, Belgium Phage-mediated metabolic changes in bacteria are hypothesized to markedly alter global nutrient and biogeochemical cycles. Despite their theoretic importance, experimental data on the net metabolic impact of phage infection on the bacterial metabolism remains scarce. In this study, we tracked the dynamics of intracellular metabolites using untargeted high coverage metabolomics in Pseudomo- nas aeruginosa cells infected with lytic bacteriophages from six distinct phage genera. Analysis of the metabolomics data indicates an active interference in the host metabolism. In general, phages elicit an increase in pyrimidine and nucleotide sugar metabolism. Furthermore, clear phage-specific and infection stage-specific responses are observed, ranging from extreme metabolite depletion (for example, phage YuA) to complete reorganization of the metabolism (for example, phage phiKZ). As expected, pathways targeted by the phage-encoded auxiliary metabolic genes (AMGs) were enriched among the metabolites changing during infection. The effect on pyrimidine metabolism of phages encoding AMGs capable of host genome degradation (for example, YuA and LUZ19) was distinct from those lacking nuclease-encoding genes (for example, phiKZ), which demonstrates the link between the encoded set of AMGs of a phage and its impact on host physiology. -
Kynurenine and Tetrahydrobiopterin Pathways Crosstalk in Pain Hypersensitivity
fnins-14-00620 June 27, 2020 Time: 15:13 # 1 REVIEW published: 24 June 2020 doi: 10.3389/fnins.2020.00620 Kynurenine and Tetrahydrobiopterin Pathways Crosstalk in Pain Hypersensitivity Ananda Staats Pires1,2, Vanessa X. Tan1, Benjamin Heng1, Gilles J. Guillemin1* and Alexandra Latini2* 1 Neuroinflammation Group, Department of Biomedical Sciences, Centre for Motor Neuron Disease Research, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia, 2 Laboratório de Bioenergética e Estresse Oxidativo, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil Despite the identification of molecular mechanisms associated with pain persistence, no Edited by: significant therapeutic improvements have been made. Advances in the understanding Marianthi Papakosta, of the molecular mechanisms that induce pain hypersensitivity will allow the Takeda Pharmaceutical Company Limited, United States development of novel, effective, and safe therapies for chronic pain. Various pro- Reviewed by: inflammatory cytokines are known to be increased during chronic pain, leading Wladyslaw-Lason, to sustained inflammation in the peripheral and central nervous systems. The Institute of Pharmacology (PAS), Poland pro-inflammatory environment activates additional metabolic routes, including the Ewa Krystyna kynurenine (KYN) and tetrahydrobiopterin (BH4) pathways, which generate bioactive Szczepanska-Sadowska, soluble metabolites with the potential to modulate neuropathic and inflammatory pain Medical University of Warsaw, Poland sensitivity. Inflammation-induced upregulation of indoleamine 2,3-dioxygenase 1 (IDO1) *Correspondence: Gilles J. Guillemin and guanosine triphosphate cyclohydrolase I (GTPCH), both rate-limiting enzymes [email protected] of KYN and BH4 biosynthesis, respectively, have been identified in experimental Alexandra Latini [email protected] chronic pain models as well in biological samples from patients affected by chronic pain. -
Defective Repression of OLE3::LUC 1 (DROL1) Is Specifically Required for the Splicing of AT–AC-Type Introns in Arabidopsis
bioRxiv preprint doi: https://doi.org/10.1101/2020.10.19.345900; this version posted October 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Defective Repression of OLE3::LUC 1 (DROL1) is specifically required for the splicing of 2 AT–AC-type introns in Arabidopsis 3 4 Takamasa Suzuki1*, Tomomi Shinagawa1, Tomoko Niwa1, Hibiki Akeda1, Satoki 5 Hashimoto1, Hideki Tanaka1, Fumiya Yamasaki1, Tsutae Kawai1, Tetsuya Higashiyama2, 3, 4, 6 Kenzo Nakamura1 7 8 1Department of Biological Chemistry, College of Bioscience and Biotechnology, Chubu 9 University, 1200 Matsumoto-cho, Kasugai, Aichi 487-8501, Japan 10 2Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, 11 Chikusa-ku, Nagoya, Aichi 464-8601, Japan; 12 3Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Aichi 13 464-8602, Japan; 14 4Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 15 Hongo, Bukyo-ku, Tokyo 113-0033, Japan 16 17 *Corresponding author: 18 Phone: +81-568-51-6369 19 Fax: +81-568-52-6594 20 E-mail: [email protected] 21 22 Running title: DROL1 specifically splice AT–AC introns 23 24 The authors responsible for distribution of materials integral to the findings presented in this 25 article in accordance with the policy described in the Instructions for Authors 26 (www.plantcell.org) are: Takamasa S. -
The Microbiota-Produced N-Formyl Peptide Fmlf Promotes Obesity-Induced Glucose
Page 1 of 230 Diabetes Title: The microbiota-produced N-formyl peptide fMLF promotes obesity-induced glucose intolerance Joshua Wollam1, Matthew Riopel1, Yong-Jiang Xu1,2, Andrew M. F. Johnson1, Jachelle M. Ofrecio1, Wei Ying1, Dalila El Ouarrat1, Luisa S. Chan3, Andrew W. Han3, Nadir A. Mahmood3, Caitlin N. Ryan3, Yun Sok Lee1, Jeramie D. Watrous1,2, Mahendra D. Chordia4, Dongfeng Pan4, Mohit Jain1,2, Jerrold M. Olefsky1 * Affiliations: 1 Division of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California, USA. 2 Department of Pharmacology, University of California, San Diego, La Jolla, California, USA. 3 Second Genome, Inc., South San Francisco, California, USA. 4 Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA. * Correspondence to: 858-534-2230, [email protected] Word Count: 4749 Figures: 6 Supplemental Figures: 11 Supplemental Tables: 5 1 Diabetes Publish Ahead of Print, published online April 22, 2019 Diabetes Page 2 of 230 ABSTRACT The composition of the gastrointestinal (GI) microbiota and associated metabolites changes dramatically with diet and the development of obesity. Although many correlations have been described, specific mechanistic links between these changes and glucose homeostasis remain to be defined. Here we show that blood and intestinal levels of the microbiota-produced N-formyl peptide, formyl-methionyl-leucyl-phenylalanine (fMLF), are elevated in high fat diet (HFD)- induced obese mice. Genetic or pharmacological inhibition of the N-formyl peptide receptor Fpr1 leads to increased insulin levels and improved glucose tolerance, dependent upon glucagon- like peptide-1 (GLP-1). Obese Fpr1-knockout (Fpr1-KO) mice also display an altered microbiome, exemplifying the dynamic relationship between host metabolism and microbiota. -
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Food & Function Accepted Manuscript This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains. www.rsc.org/foodfunction Page 1 of 16 PleaseFood do not & Functionadjust margins Food&Function REVIEW ARTICLE Interactions between acrylamide, microorganisms, and food components – a review. Received 00th January 20xx, a† a a a a Accepted 00th January 20xx A. Duda-Chodak , Ł. Wajda , T. Tarko , P. Sroka , and P. Satora DOI: 10.1039/x0xx00000x Acrylamide (AA) and its metabolites have been recognised as potential carcinogens, but also they can cause other negative symptoms in human or animal organisms so this chemical compounds still attract a lot of attention. Those substances are www.rsc.org/ usually formed during heating asparagine in the presence of compounds that have α-hydroxycarbonyl groups, α,β,γ,δ- diunsaturated carbonyl groups or α-dicarbonyl groups. -
Discovery of a New Genetic Variant of Methionine Aminopeptidase From
Discovery of a New Genetic Variant of Methionine Aminopeptidase from Streptococci with Possible Post- Translational Modifications: Biochemical and Structural Characterization Tarun Arya, Chandan Kishor, Venkateshwarlu Saddanapu, Ravikumar Reddi, Anthony Addlagatta* Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, Andhra Pradesh, India Abstract Protein N-terminal methionine excision is an essential co-translational process that occurs in the cytoplasm of all organisms. About 60-70% of the newly synthesized proteins undergo this modification. Enzyme responsible for the removal of initiator methionine is methionine aminopeptidase (MetAP), which is a dinuclear metalloprotease. This protein is conserved through all forms of life from bacteria to human except viruses. MetAP is classified into two isoforms, Type I and II. Removal of the map gene or chemical inhibition is lethal to bacteria and to human cell lines, suggesting that MetAP could be a good drug target. In the present study we describe the discovery of a new genetic variant of the Type I MetAP that is present predominantly in the streptococci bacteria. There are two inserts (insert one: 27 amino acids and insert two: four residues) within the catalytic domain. Possible glycosylation and phosphorylation posttranslational modification sites are identified in the ‘insert one’. Biochemical characterization suggests that this enzyme behaves similar to other MetAPs in terms of substrate specificity. Crystal structure Type Ia MetAP from Streptococcus pneumoniae (SpMetAP1a) revealed that it contains two molecules in the asymmetric unit and well ordered inserts with structural features that corroborate the possible posttranslational modification. Both the new inserts found in the SpMetAP1a structurally align with the P-X-X-P motif found in the M.