DOCSLIB.ORG

Recent Insight in Α-Glucan Metabolism in Probiotic Bacteria

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Recent Insight in Α-Glucan Metabolism in Probiotic Bacteria Biologia 69/6: 713—721, 2014 Section Cellular and Molecular Biology DOI: 10.2478/s11756-014-0367-7 Review Recent insight in α-glucan metabolism in probiotic bacteria Marie S. Møller1,YongJunGoh2, Alexander H. Viborg1,Joakim M. Andersen1, Todd R. Klaenhammer2,BirteSvensson1 &MaherAbou Hachem1* 1Enzyme and Protein Chemistry, Department of Systems Biology, Technical University of Denmark, Søltofts Plads, Building 224,DK-2800 Kgs. Lyngby, Denmark; e-mail: [email protected] 2Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Box 7624, Raleigh, NC 27695 USA Abstract: α-Glucans from bacterial exo-polysaccharides or diet, e.g., resistant starch, legumes and honey are abundant in the human gut and fermentation of resistant fractions of these α-glucans by probiotic lactobacilli and bifidobacteria impacts human health positively. The ability to degrade polymeric α-glucans is confined to few strains encoding extra- cellular amylolytic activities of glycoside hydrolase (GH) family 13. Debranching pullulanases of the subfamily GH13 14 are the most common extracellular GH13 enzymes in lactobacilli, whereas corresponding enzymes are mainly α-amylases and amylopullulanases in bifidobacteria. Extracellular GH13 enzymes from both genera are frequently modular and pos- sess starch binding domains, which are important for efficient catalysis and possibly to mediate attachment of cells to starch granules. α-1,6-Linked glucans, e.g., isomalto-oligosaccharides are potential prebiotics. The enzymes targeting these glucans are the most abundant intracellular GHs in bifidobacteria and lactobacilli. A phosphoenolpyruvate-dependent phos- photransferase system and a GH4 phospho-α-glucosidase are likely involved in metabolism of isomaltose and isomaltulose in probiotic lactobacilli based on transcriptional analysis. This specificity within GH4 is unique for lactobacilli, whereas canonical GH13 31 α-1,6-glucosidases active on longer α-1,6-gluco-oligosaccharides are ubiquitous in bifidobacteria and lactobacilli. Malto-oligosaccharide utilization operons encode more complex, diverse, and less biochemically understood ac- tivities in bifidobacteria compared to lactobacilli, where important members have been recently described at the molecular level. This review presents some aspects of α-glucan metabolism in probiotic bacteria and highlights vague issues that merit experimental effort, especially oligosaccharide uptake and the functionally unassigned enzymes, featuring in this important facet of glycan turnover by members of the gut microbiota. Key words: prebiotic; oligosaccharide uptake; ATP-binding cassette transport system; phosphotransferase system; tran- scriptional analysis; isomalto-oligosaccharide; malto-oligosaccharide. Abbreviations: ABC, ATP-binding cassette; CAZy, Carbohydrate-Active enZymes database; CBM, carbohydrate binding module; GH, glycoside hydrolase; GI, gastrointestinal tract; GT, glycosyl transferase family; IMO, isomaltooligosaccharide; PTS, phosphotransferase transport system; RS, resistant starch. Introduction gut microbiota is dominated by mainly four bacterial phyla with Firmicutes being the most abundant fol- The intimate association between microbes and humans lowed by Bacteroidetes, Actinobacteria and Proteobac- (and other animals) has been increasingly recognized teria (Arumugam et al. 2011). This lower complexity at as a major factor affecting the co-evolution, physiol- phylum level belies the true diversity of the gut micro- ogy, and metabolic interplay between both classes of biota, that comprises an excess of 100 species (varies ac- organisms (Ley et al. 2008; McFall-Ngai et al. 2013). cording to study and protocol used) (Faith et al. 2013) Humans consist of their own somatic cells only until and which is unique to each individual. Common to birth, but in conjunction with delivery the newborn all humans, however, is that imbalance in the gut mi- are inoculated with microbes that proliferate to estab- crobiota (dysbiosis) as compared to the status-quo at- lish vast and complex communities in the gastrointesti- tained in the early years of life, is associated with seri- nal tracts (GI) and at other sites of the body. The ous disorders including obesity, diabetes, bowel cancer, gut microbial community develops rapidly in the new- and allergies ( Wallace et al. 2011; Kootte et al. 2012; born and stabilizes after two to three years (Morgan et Sommer & Baeckhed 2012). The precise composition al. 2013), forming one of the most densely populated of the gut microbiota is governed by a variety of fac- ecological niches in nature (Eckburg et al. 2005). The tors, e.g., age, genetics, method of delivery and lifestyle * Corresponding author c 2014 Institute of Molecular Biology, Slovak Academy of Sciences 714 M.S. Møller et al. (Nicholson et al. 2012). Despite the apparent stability α-1,6-gluco-oligosaccharides possess prebiotic poten- of the gut microbiota through adulthood, it remains dy- tial as judged by preferential stimulation of probi- namic being able to respond to perturbations through otic bacteria and improved bowel function (Kaneko et changes in its composition reflected at the species level al. 1994, Yen et al. 2011). Additionally, a recent re- and in the ratio between different phyla, which has been port suggests that RS resulted in significant increase demonstrated to be of significance to health and dis- in lactic acid production and a change in the Bac- ease risks (Clemente et al. 2012). An obvious example teroidetes/Firmicutes ratio in fecal in vitro fermen- of such perturbations is changes in diet, which has been tations, supplemented with the probiotic strain Lac- shown to alter the composition of the microbiota (Scott tobacillus acidophilus NCFM (Knudsen et al. 2013). et al. 2013). These data are consistent with the importance of α- Humans possess remarkably limited saccharolytic glucan metabolism in probiotic bacteria, which is also machinery being only able to hydrolyze glycosidic reflected by the notably high representation of glyco- bonds in sucrose, lactose and to a certain extent starch side hydrolase (GH) family 13 genes that are pivotal in by their digestive enzymes (Cantarel et al. 2012), ren- α-glucan metabolism by probiotic bacteria as compared dering most glycans essentially non-digestible to hu- to other GH families according to the mechanism and mans. On the other hand, human diet contains large sequence-based Carbohydrate-Active enZymes (CAZy) quantities of glycans in cereals, fruits and vegetables, classification system (http://www.cazy.org/) (Cantarel most of which reach the distal gut (colon) intact and are et al. 2009). harvested by the gut microbiota to generate metabolic Considering the importance of probiotic bacteria fuel. This is in accord with the important role that gly- in the context of human health and the interest in non- can metabolism plays in modulating the composition of invasive manipulation of the gut microbiota compo- the gut microbiota, and the inherent impact of this on sition for therapeutic purposes, surprisingly little at- health (Lozupone et al. 2008; Muegge et al. 2011; Scott tention has been dedicated to α-glucan metabolism et al. 2013). in probiotic bacteria and many aspects of this part Starch, which is an exclusively α-glucan polymer of their glycan metabolism remain ill-understood. In organized in supramolecular insoluble semicrystalline the present review, we survey the content of GH13 granules (Tester et al. 2004), is the most abundant gly- in genomes of genera harbouring probiotic strains and can in human diet. Although humans possess the en- highlight recent insight into the routes of uptake and zymatic machinery for starch breakdown (mainly the metabolism of selected α-glucans. Recent work on α-1,4-glycosidic bonds), the degradability of this poly- glycogen metabolism in probiotic lactobacilli, which is mer varies considerably based on botanic origin and fine of relevance to fitness in the highly competitive and structural details, especially crystal-packing (Blazek & dynamic niche of the gut is also presented. Gilbert 2010). Thus, significant amounts of dietary re- sistant starch (RS) reach the distal colon where they are A genomic survey of GH13 α-glucan active fermented by members of the gut microbiota (Fuentes- CAZymes in Lactobacillus and Bifidobacterium: Zaragoza et al. 2011). Other dietary sources of α- a snapshot into α-glucan metabolism potential glucans likely to reach the colon intact are α-1,6- linked gluco-oligosaccharides (often designated as iso- At present, the family GH13 includes the vast major- maltooligosaccharides; IMOs) from legumes and honey ity of α-glucan-active enzymes in the CAZy database (Goffin et al. 2011), as these glucans are non-digestible (>15,800 sequences), making this family a good probe for humans except for the disaccharide isomaltose (α- for metabolic capabilities in relation to α-glucans. d-Glcp-(1,6)-d-Glcp). Beside dietary intake, capsular This section focuses on the distribution of the GH13 polysaccharides or exo-polysaccharides produced by CAZymes in the Lactobacillus and Bifidobacterium, members of the gut bacterial community (Duboc & which casts light on the commonalities and differences Mollet 2001) (or acquired via bacterial food contam- in the enzymology of α-glucan processing from a ge- inants) comprise another class of α-glucan substrates nomic perspective. Other selected CAZy families with that are available to support bacterial growth in the important activities relevant to α-glucan metabolism
Load more

Recommended publications
  • Bacteria Belonging to Pseudomonas Typographi Sp. Nov. from the Bark Beetle Ips Typographus Have Genomic Potential to Aid in the Host Ecology
    insects Article Bacteria Belonging to Pseudomonas typographi sp. nov. from the Bark Beetle Ips typographus Have Genomic Potential to Aid in the Host Ecology Ezequiel Peral-Aranega 1,2 , Zaki Saati-Santamaría 1,2 , Miroslav Kolaˇrik 3,4, Raúl Rivas 1,2,5 and Paula García-Fraile 1,2,4,5,* 1 Microbiology and Genetics Department, University of Salamanca, 37007 Salamanca, Spain; [email protected] (E.P.-A.); [email protected] (Z.S.-S.); [email protected] (R.R.) 2 Spanish-Portuguese Institute for Agricultural Research (CIALE), 37185 Salamanca, Spain 3 Department of Botany, Faculty of Science, Charles University, Benátská 2, 128 01 Prague, Czech Republic; [email protected] 4 Laboratory of Fungal Genetics and Metabolism, Institute of Microbiology of the Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic 5 Associated Research Unit of Plant-Microorganism Interaction, University of Salamanca-IRNASA-CSIC, 37008 Salamanca, Spain * Correspondence: [email protected] Received: 4 July 2020; Accepted: 1 September 2020; Published: 3 September 2020 Simple Summary: European Bark Beetle (Ips typographus) is a pest that affects dead and weakened spruce trees. Under certain environmental conditions, it has massive outbreaks, resulting in attacks of healthy trees, becoming a forest pest. It has been proposed that the bark beetle’s microbiome plays a key role in the insect’s ecology, providing nutrients, inhibiting pathogens, and degrading tree defense compounds, among other probable traits. During a study of bacterial associates from I. typographus, we isolated three strains identified as Pseudomonas from different beetle life stages. In this work, we aimed to reveal the taxonomic status of these bacterial strains and to sequence and annotate their genomes to mine possible traits related to a role within the bark beetle holobiont.
    [Show full text]
  • Structure and Function of a Glycoside Hydrolase Family 8 Endoxylanase from Teredinibacter Turnerae
    This is a repository copy of Structure and function of a glycoside hydrolase family 8 endoxylanase from Teredinibacter turnerae. White Rose Research Online URL for this paper: https://eprints.whiterose.ac.uk/137106/ Version: Published Version Article: Fowler, Claire A, Hemsworth, Glyn R orcid.org/0000-0002-8226-1380, Cuskin, Fiona et al. (5 more authors) (2018) Structure and function of a glycoside hydrolase family 8 endoxylanase from Teredinibacter turnerae. Acta crystallographica. Section D, Structural biology. pp. 946-955. ISSN 2059-7983 https://doi.org/10.1107/S2059798318009737 Reuse This article is distributed under the terms of the Creative Commons Attribution (CC BY) licence. This licence allows you to distribute, remix, tweak, and build upon the work, even commercially, as long as you credit the authors for the original work. More information and the full terms of the licence here: https://creativecommons.org/licenses/ Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ research papers Structure and function of a glycoside hydrolase family 8 endoxylanase from Teredinibacter turnerae ISSN 2059-7983 Claire A. Fowler,a Glyn R. Hemsworth,b Fiona Cuskin,c Sam Hart,a Johan Turkenburg,a Harry J. Gilbert,d Paul H. Waltone and Gideon J. Daviesa* aYork Structural Biology Laboratory, Department of Chemistry, The University of York, York YO10 5DD, England, b Received 20 March 2018 School of Molecular and Cellular Biology, The Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, c Accepted 9 July 2018 England, School of Natural and Environmental Science, Newcastle University, Newcastle upon Tyne NE1 7RU, England, dInstitute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, England, and eDepartment of Chemistry, The University of York, York YO10 5DD, England.
    [Show full text]
  • 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)
    [Show full text]
  • Mannoside Recognition and Degradation by Bacteria Simon Ladeveze, Elisabeth Laville, Jordane Despres, Pascale Mosoni, Gabrielle Veronese
    Mannoside recognition and degradation by bacteria Simon Ladeveze, Elisabeth Laville, Jordane Despres, Pascale Mosoni, Gabrielle Veronese To cite this version: Simon Ladeveze, Elisabeth Laville, Jordane Despres, Pascale Mosoni, Gabrielle Veronese. Mannoside recognition and degradation by bacteria. Biological Reviews, Wiley, 2016, 10.1111/brv.12316. hal- 01602393 HAL Id: hal-01602393 https://hal.archives-ouvertes.fr/hal-01602393 Submitted on 26 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Biol. Rev. (2016), pp. 000–000. 1 doi: 10.1111/brv.12316 Mannoside recognition and degradation by bacteria Simon Ladeveze` 1, Elisabeth Laville1, Jordane Despres2, Pascale Mosoni2 and Gabrielle Potocki-Veron´ ese` 1∗ 1LISBP, Universit´e de Toulouse, CNRS, INRA, INSA, 31077, Toulouse, France 2INRA, UR454 Microbiologie, F-63122, Saint-Gen`es Champanelle, France ABSTRACT Mannosides constitute a vast group of glycans widely distributed in nature. Produced by almost all organisms, these carbohydrates are involved in numerous cellular processes, such as cell structuration, protein maturation and signalling, mediation of protein–protein interactions and cell recognition. The ubiquitous presence of mannosides in the environment means they are a reliable source of carbon and energy for bacteria, which have developed complex strategies to harvest them.
    [Show full text]
  • Structure of Human Endo-Α-1,2-Mannosidase (MANEA), an Antiviral Host- Glycosylation Target
    bioRxiv preprint doi: https://doi.org/10.1101/2020.06.30.179523; this version posted July 1, 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 CLASSIFICATION: Biological Sciences / Physical Sciences (Chemistry) TITLE: Structure of human endo-α-1,2-mannosidase (MANEA), an antiviral host- glycosylation target AUTHORS: Łukasz F. Sobala1, Pearl Z Fernandes2, Zalihe Hakki2, Andrew J Thompson1, Jonathon D Howe3, Michelle Hill3, Nicole Zitzmann3, Scott Davies4, Zania Stamataki4, Terry D. Butters3, Dominic S. Alonzi3, Spencer J Williams2,*, Gideon J Davies1,* AFFILIATIONS: 1. Department of Chemistry, University of York, YO10 5DD, United Kingdom. 2. School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia. 3. Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road Oxford OX1 3QU, United Kingdom. 4. Institute for Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom. CORRESPONDING AUTHOR: [email protected], ORCID 0000-0001-6341-4364 [email protected] ORCID 0000-0002-7343-776X bioRxiv preprint doi: https://doi.org/10.1101/2020.06.30.179523; this version posted July 1, 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.
    [Show full text]
  • Structural and Functional Studies of Glycoside Hydrolase Family 12 Enzymes from Trichoderma Reesei and Other Cellulolytic Microorganisms
    Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 819 Structural and Functional Studies of Glycoside Hydrolase Family 12 Enzymes from Trichoderma reesei and other Cellulolytic Microorganisms BY MATS SANDGREN ACTA UNIVERSITATIS UPSALIENSIS UPPSALA 2003 Dissertation for the Degree of Doctor of Philosophy in Molecular Biology presented at Uppsala University in 2003. ABSTRACT Sandgren, M. 2003. Structural and functional studies of glycoside hydrolase family 12 enzymes from Trichoderma reesei and other cellulolytic microorganisms. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations from the faculty of Science and Technology 819. 68 pp. Uppsala. ISBN 91-554-5562-X Cellulose is the most abundant organic compound on earth. A wide range of highly specialized microorganisms, have evolved that utilize cellulose as carbon and energy source. Enzymes called cellulases, produced by these cellulolytic organisms, perform the major part of cellulose degradation. In this study the three-dimensional structure of four homologous glycoside hydrolase family 12 cellulases will be presented, three fungal enzymes; Humicola grisea Cel12A, Hypocrea schweinitzii Cel12A, Trichoderma reesei Cel12A, and one bacterial; Streptomyces sp. 11AG8 Cel12A. The structural and biochemical information gathered from these and 15 other GH family 12 homologues has been used for the design of variants of these enzymes. These variants have biochemically been characterized, and thereby the positions and the types of mutations have been identified responsible for the biochemical differences between the homologous enzymes, e.g., thermal stability and activity. The three-dimensional structures of two T. reesei Cel12A variants, where the mutations have significant impact on the stability or the activity of the enzyme have been determined.
    [Show full text]
  • Glycoside Hydrolase Stabilization of Transition State Charge: New Directions for Inhibitor Design† Cite This: Chem
    Chemical Science View Article Online EDGE ARTICLE View Journal | View Issue Glycoside hydrolase stabilization of transition state charge: new directions for inhibitor design† Cite this: Chem. Sci., 2020, 11, 10488 a a a b All publication charges for this article Weiwu Ren, ‡ Marco Farren-Dai, Natalia Sannikova, Katarzyna Swiderek,´ have been paid for by the Royal Society Yang Wang, ‡a Oluwafemi Akintola, a Robert Britton, *a Vicent Moliner *b of Chemistry and Andrew J. Bennet *a Carbasugars are structural mimics of naturally occurring carbohydrates that can interact with and inhibit enzymes involved in carbohydrate processing. In particular, carbasugars have attracted attention as inhibitors of glycoside hydrolases (GHs) and as therapeutic leads in several disease areas. However, it is unclear how the carbasugars are recognized and processed by GHs. Here, we report the synthesis of three carbasugar isotopologues and provide a detailed transition state (TS) analysis for the formation of the initial GH-carbasugar covalent intermediate, as well as for hydrolysis of this intermediate, using a combination of experimentally measured kinetic isotope effects and hybrid QM/MM calculations. We find that the a-galactosidase from Thermotoga maritima effectively stabilizes TS charge development on Creative Commons Attribution-NonCommercial 3.0 Unported Licence. a remote C5-allylic center acting in concert with the reacting carbasugar, and catalysis proceeds via an exploded, or loose, SN2 transition state with no discrete enzyme-bound cationic intermediate. We conclude that, in complement to what we know about the TS structures of enzyme-natural substrate Received 10th August 2020 complexes, knowledge of the TS structures of enzymes reacting with non-natural carbasugar substrates Accepted 16th September 2020 shows that GHs can stabilize a wider range of positively charged TS structures than previously thought.
    [Show full text]
  • Microbial Beta Glucosidase Enzymes: Recent Advances in Biomass Conversation for Biofuels Application
    biomolecules Review Microbial Beta Glucosidase Enzymes: Recent Advances in Biomass Conversation for Biofuels Application 1, , 2 3 1 4, Neha Srivastava * y, Rishabh Rathour , Sonam Jha , Karan Pandey , Manish Srivastava y, Vijay Kumar Thakur 5,* , Rakesh Singh Sengar 6, Vijai K. Gupta 7,* , Pranab Behari Mazumder 8, Ahamad Faiz Khan 2 and Pradeep Kumar Mishra 1,* 1 Department of Chemical Engineering and Technology, IIT (BHU), Varanasi 221005, India; [email protected] 2 Department of Bioengineering, Integral University, Lucknow 226026, India; [email protected] (R.R.); [email protected] (A.F.K.) 3 Department of Botany, Banaras Hindu University, Varanasi 221005, India; [email protected] 4 Department of Physics and Astrophysics, University of Delhi, Delhi 110007, India; [email protected] 5 Enhanced Composites and Structures Center, School of Aerospace, Transport and Manufacturing, Cranfield University, Bedfordshire MK43 0AL, UK 6 Department of Agriculture Biotechnology, College of Agriculture, Sardar Vallabhbhai Patel, University of Agriculture and Technology, Meerut 250110, U.P., India; [email protected] 7 Department of Chemistry and Biotechnology, ERA Chair of Green Chemistry, Tallinn University of Technology, 12618 Tallinn, Estonia 8 Department of Biotechnology, Assam University, Silchar 788011, India; [email protected] * Correspondence: [email protected] (N.S.); vijay.Kumar@cranfield.ac.uk (V.K.T.); [email protected] (V.K.G.); [email protected] (P.K.M.); Tel.: +372-567-11014 (V.K.G.); Fax: +372-620-4401 (V.K.G.) These authors have equal contribution. y Received: 29 March 2019; Accepted: 28 May 2019; Published: 6 June 2019 Abstract: The biomass to biofuels production process is green, sustainable, and an advanced technique to resolve the current environmental issues generated from fossil fuels.
    [Show full text]
  • 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.
    [Show full text]
  • Action of Multiple Rice -Glucosidases on Abscisic Acid Glucose Ester
    International Journal of Molecular Sciences Article Action of Multiple Rice β-Glucosidases on Abscisic Acid Glucose Ester Manatchanok Kongdin 1, Bancha Mahong 2, Sang-Kyu Lee 2, Su-Hyeon Shim 2, Jong-Seong Jeon 2,* and James R. Ketudat Cairns 1,* 1 School of Chemistry, Institute of Science, Center for Biomolecular Structure, Function and Application, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand; [email protected] 2 Graduate School of Biotechnology and Crop Biotech Institute, Kyung Hee University, Yongin 17104, Korea; [email protected] (B.M.); [email protected] (S.-K.L.); [email protected] (S.-H.S.) * Correspondence: [email protected] (J.-S.J.); [email protected] (J.R.K.C.); Tel.: +82-31-2012025 (J.-S.J.); +66-44-224304 (J.R.K.C.); Fax: +66-44-224185 (J.R.K.C.) Abstract: Conjugation of phytohormones with glucose is a means of modulating their activities, which can be rapidly reversed by the action of β-glucosidases. Evaluation of previously characterized recombinant rice β-glucosidases found that nearly all could hydrolyze abscisic acid glucose ester (ABA-GE). Os4BGlu12 and Os4BGlu13, which are known to act on other phytohormones, had the highest activity. We expressed Os4BGlu12, Os4BGlu13 and other members of a highly similar rice chromosome 4 gene cluster (Os4BGlu9, Os4BGlu10 and Os4BGlu11) in transgenic Arabidopsis. Extracts of transgenic lines expressing each of the five genes had higher β-glucosidase activities on ABA-GE and gibberellin A4 glucose ester (GA4-GE). The β-glucosidase expression lines exhibited longer root and shoot lengths than control plants in response to salt and drought stress.
    [Show full text]
  • Biochemical Characterization of Β-Xylan Acting Glycoside
    BIOCHEMICAL CHARACTERIZATION OF β-XYLAN ACTING GLYCOSIDE HYDROLASES FROM THE THERMOPHILIC BACTERIUM Caldicellulosiruptor saccharolyticus Thesis Submitted to The School of Engineering of the UNIVERSITY OF DAYTON In Partial Fulfillment of the Requirements for The Degree of Master of Science in Chemical Engineering By Jin Cao Dayton, Ohio December, 2012 BIOCHEMICAL CHARACTERIZATION OF β-XYLAN ACTING GLYCOSIDE HYDROLASES FROM THE THERMOPHILIC BACTERIUM Caldicellulosiruptor saccharolyticus Name: Cao, Jin APPROVED BY: ______________________ ________________________ Donald A. Comfort, Ph.D. Amy Ciric, Ph.D. Advisory Committee Chairman Committee Member Research Advisor & Assistant Professor Lecturer Department of Department of Chemical & Materials Engineering Chemical & Materials Engineering ________________________ Karolyn Hansen, Ph.D. Committee Member Assistant Professor Department of Biology _______________________ ________________________ John G. Weber, Ph.D. Tony E. Saliba, Ph.D. Associate Dean Dean, School of Engineering School of Engineering & Wilke Distinguished Professor ii ABSTRACT BIOCHEMICAL CHARACTERIZATION OF Β-XYLAN ACTING GLYCOSIDE HYDROLASES FROM THE THERMOPHILIC BACTERIUM Caldicellulosiruptor saccharolyticus Name: Cao, Jin University of Dayton Research Advisor: Donald A. Comfort Fossil fuels have been the dominant source for energy around the world since the industrial revolution, however, with the increasing demand for energy and decreasing fossil fuel reserves alternative energy sources must be exploited. Bio-ethanol is a promising prospect for an alternative energy source to petroleum, especially when plant biomass is used as the replacement carbon source. This gives greater benefit for implementation of bioethanol as a viable alternative transport fuel than food stocks such as starch from corn. The implementation of this next generation of bioethanol requires more robust and environmentally friendly methods for degrading cellulose and hemicellulose, the two major components of plant biomass.
    [Show full text]
  • Protein & Peptide Letters
    696 Send Orders for Reprints to [email protected] Protein & Peptide Letters, 2017, 24, 696-709 REVIEW ARTICLE ISSN: 0929-8665 eISSN: 1875-5305 Impact Factor: 1.068 Glycan Phosphorylases in Multi-Enzyme Synthetic Processes BENTHAM Editor-in-Chief: SCIENCE Ben M. Dunn Giulia Pergolizzia, Sakonwan Kuhaudomlarpa, Eeshan Kalitaa,b and Robert A. Fielda,* aDepartment of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK; bDepartment of Molecular Biology and Biotechnology, Tezpur University, Napaam, Tezpur, Assam -784028, India Abstract: Glycoside phosphorylases catalyse the reversible synthesis of glycosidic bonds by glyco- A R T I C L E H I S T O R Y sylation with concomitant release of inorganic phosphate. The equilibrium position of such reac- tions can render them of limited synthetic utility, unless coupled with a secondary enzymatic step Received: January 17, 2017 Revised: May 24, 2017 where the reaction lies heavily in favour of product. This article surveys recent works on the com- Accepted: June 20, 2017 bined use of glycan phosphorylases with other enzymes to achieve synthetically useful processes. DOI: 10.2174/0929866524666170811125109 Keywords: Phosphorylase, disaccharide, α-glucan, cellodextrin, high-value products, biofuel. O O 1. INTRODUCTION + HO OH Glycoside phosphorylases (GPs) are carbohydrate-active GH enzymes (CAZymes) (URL: http://www.cazy.org/) [1] in- H2O O GP volved in the formation/cleavage of glycosidic bond together O O GT O O + HO O + HO with glycosyltransferase (GT) and glycoside hydrolase (GH) O -- NDP OPO3 NDP -- families (Figure 1) [2-6]. GT reactions favour the thermody- HPO4 namically more stable glycoside product [7]; however, these GS R enzymes can be challenging to work with because of their O O + HO current limited availability and relative instability, along R with the expense of sugar nucleotide substrates [7].
    [Show full text]