DOCSLIB.ORG

L-Fucose Utilization Provides Campylobacter Jejuni with a Competitive Advantage

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
L-Fucose Utilization Provides Campylobacter Jejuni with a Competitive Advantage L-Fucose utilization provides Campylobacter jejuni with a competitive advantage Martin Stahla, Lorna M. Friisb,1, Harald Nothaftb,1, Xin Liuc, Jianjun Lic, Christine M. Szymanskib,2, and Alain Stintzia,2 aOttawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada K1H 8M5; bAlberta Ingenuity Centre for Carbohydrate Science, Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada T6G 2E9; and cInstitute for Biological Sciences, National Research Council, Ottawa, ON, Canada K1A 0R6 Edited* by Pascale Cossart, Institut Pasteur, Paris, France, and approved March 18, 2011 (received for review September 23, 2010) Campylobacter jejuni is a prevalent gastrointestinal pathogen in typically located in terminal positions on the extensively modi- humans and a common commensal of poultry. When colonizing fied mucin glycoproteins (13, 15). These fucosylated glycans coating its hosts, C. jejuni comes into contact with intestinal carbohydrates, the mucins are known to act as adherence targets for many in- including L-fucose, released from mucin glycoproteins. Several testinal bacteria [including C. jejuni (16)], potentially contributing strains of C. jejuni possess a genomic island (cj0480c–cj0490) that to the function of mucin as a barrier to intestinal pathogens (17). is up-regulated in the presence of both L-fucose and mucin and Fucose monomers and fucosylated glycans can serve as a chemo- allows for the utilization of L-fucose as a substrate for growth. attractant (18) and carbon source for many species within the gut. Strains possessing this genomic island show increased growth in Being so common within the intestine, fucose is an integral part of the presence of L-fucose and mutation of cj0481, cj0486, and the intestinal ecology. For example, the presence of the ubiqui- cj0487 results in the loss of the ability to grow on this substrate. tous commensal Bacteroides thetaiotaomicron in the gut triggers Furthermore, mutants in the putative fucose permease (cj0486) are an increase in the production of fucosylated mucins by the in- deficient in fucose uptake and demonstrate a competitive disadvan- testinal epithelium, which is important for gut maturation (19). tage when colonizing the piglet model of human disease, which is These bacteria then secrete fucosidases to release fucose residues not paralleled in the colonization of poultry. This identifies a previ- from the oligosaccharides and transport the sugar into the cell ously unrecorded metabolic pathway in select strains of C. jejuni for metabolism and surface presentation (12, 20). Even bacteria associated with a virulent lifestyle. such as Escherichia coli, which do not express fucosidases, use this MICROBIOLOGY same pathway for fucose transport (21) and colonization of the pathogenesis | metabolism | gut | mucus bovine rectum (22). Despite the lack of an annotated fucose metabolic pathway, he most common cause of gastroenteritis in the developed fucose has long been described as influencing the behavior of C. Tworld, Campylobacter jejuni is a frequent cause of pediatric jejuni. In 1988, Hugdahl et al. reported C. jejuni chemotaxis to- diarrheal episodes within developing countries that can last from ward L-fucose, as well as toward intact mucins, which would have a few days to several weeks (1). The symptoms vary from mild, included fucosylated glycans (18). In addition, fucosylated milk watery diarrhea to bloody diarrhea with fever and severe abdom- oligosaccharides were used in an elegant experiment to com- inal pain (2). The disease usually resolves itself relatively quickly, petitively inhibit the specific attachment of C. jejuni to intestinal but autoimmune reactions to the infection can lead to post- H-antigens (23). More recently, Korolik and colleagues have infectious sequelae, such as Guillain-Barré syndrome and reactive made use of glycan microarrays to demonstrate increased C. arthritis (2). jejuni adherence to fucosylated glycans, such as those found on When colonizing its host (whether commensally in poultry and mucin and cell surfaces (16), structures that were suggested to be other animals, or pathogenically in humans), C. jejuni must es- significant factors in the ability of C. jejuni to closely adhere to tablish itself within the mucus layer of the intestinal epithelium (3, the cell surface and invade intestinal epithelial cells. 4). Byrne et al. (5) recently showed that the mucus layer originating This study is unique in demonstrating the uptake and utilization from humans or chickens influences the virulence of C. jejuni and of L-fucose by certain strains of C. jejuni via a previously unde- might differentially control the virulence versus commensalism scribed pathway not found in other enteric bacteria. We further equilibrium. However, it remains unknown which specific com- demonstrate how L-fucose transport provides a distinct competi- ponents of the mucus layer contribute to this change in phenotype. tive advantage in the pathogenesis model that is not found during C. jejuni lacks many of the pathways for nutrient metabolism commensal growth. used by other pathogens and the normal intestinal microbiota. Results For example, several key enzymes within the glycolytic pathway, the Entner-Doudoroff pathway, and the pentose phosphate Fucose Up-Regulates Expression of Genes Linked to Fucose Use. pathway are absent (6, 7), and it has generally been assumed that Microarray experiments were used to assemble a transcriptomic fi C. jejuni α C. jejuni is unable to use any form of carbohydrate as a substrate pro le of NCTC 11168 during growth in MEM medium for growth. Instead, C. jejuni relies on the use of amino acids and citric acid cycle intermediates as carbon sources (8). The amino acid metabolic pathways that allow C. jejuni to use serine (9), Author contributions: M.S., L.M.F., H.N., J.L., C.M.S., and A.S. designed research; M.S., L.M.F., H.N., X.L., and J.L. performed research; M.S., L.M.F., H.N., X.L., J.L., C.M.S., and A.S. analyzed aspartate, glutamate (10), and proline (11) have all been studied data; and M.S., L.M.F., H.N., C.M.S., and A.S. wrote the paper. C. jejuni – in depth. Additionally, some strains, including 81 176, The authors declare no conflict of interest. can metabolize glutamine and asparagine (8). However, and in *This Direct Submission article had a prearranged editor. contrast to the generally accepted paradigm, we demonstrate in C. jejuni Data deposition: The microarray data have been deposited in the National Center for this study that certain strains of contain a unique path- Biotechnology Information Geo Omnibus database. way for the uptake and metabolism of the sugar L-fucose, which is 1L.M.F. and H.N. contributed equally to this work. obtained from the host during colonization of the intestine. 2To whom correspondence may be addressed. E-mail: [email protected] or cszymans@ The importance of fucose to the intestinal microflora is well ualberta.ca. – established (12 14). Fucosylated glycans are common within the This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. digestive tract, where they are found on cell surfaces and are 1073/pnas.1014125108/-/DCSupplemental. www.pnas.org/cgi/doi/10.1073/pnas.1014125108 PNAS Early Edition | 1of6 Downloaded by guest on September 27, 2021 supplemented with 25 mM L-fucose. This process led to the tator superfamily (MFS) transporter, but does not contain these identification of 74 up-regulated genes, and 52 down-regulated conserved residues or a significant degree of sequence similarity, genes (Table S1). The most notable change from the list of up- suggesting it does not serve as a second L-fucose transporter. 3 regulated genes was an operon between cj0481 and cj0490, which Active transport of L-fucose by C. jejuni was confirmed in H-L- exhibited six- to -ninefold up-regulation (Table S1). The putative fucose uptake experiments. In wild-type cells grown in the absence regulator cj0480c did not show any significant change in expres- of L-fucose, the initial uptake was approximately threefold lower sion. Similarly, a microarray study of C. jejuni grown in MEMα than in cells grown in the presence of L-fucose (Fig. 2A), consistent medium supplemented with 2 mg/mL porcine gastric mucin also with E. coli (Fig. 2B), indicating that [3H]-fucose transport is in- revealed significant up-regulation (two- to fourfold) of the genes ducible by its substrate. Insertion mutants were subsequently cj0481 to cj0490 (Table S2). constructed into C. jejuni genes cj0481, cj0483, cj0486,andcj0487. The Δcj0486 mutant (Fig. 2) showed no significant fucose transport fi Identi cation of a Genomic Island Required for Fucose Utilization. (< 0.2 pmols·min·109 cfu), demonstrating that Cj0486 is an es- cj0480c cj0490 fi None of the genes to have any con rmed func- sential component of the active L-fucose assimilation pathway in C. tion, but cj0486 bears homology to the fucose permease gene jejuni cj0481 cj0483 cj0487 fucP fi . The mutants , , and all transport L-fu- ( ) of other bacteria (21). This operon has been identi ed cose at levels of the uniduced wild-type strain independent of the previously in RM1221 and NCTC 11168 as a genomic island presence of fucose in the growth medium. This finding indicates spanning from cj0480c to cj0490 (24) and nestled in between the rpoC fusA that fucose transport is still occurring but not inducible in these genes and (Fig. S1) of some strains. Notably, this re- strains (Fig. 2A). Complementation of cj0486 and cj0487 showed gion is absent in strain 81–176. Although this region is not uni- partial, but significant, restoration of L-fucose uptake. Quantitative versally conserved within strains of C. jejuni, it has been linked to RT-PCR analysis demonstrated that cj0486 and cj0487 are ex- C. jejuni hyper-invasiveness (25, 26). pressed at <11% of the wild-type levels in the complemented In a comparison of the amino acid sequence of Cj0486 among Campylobacter C.
Load more

Recommended publications
  • Enzymatic Synthesis of L-Fucose from L-Fuculose Using a Fucose Isomerase
    Kim et al. Biotechnol Biofuels (2019) 12:282 https://doi.org/10.1186/s13068-019-1619-0 Biotechnology for Biofuels RESEARCH Open Access Enzymatic synthesis of L-fucose from L-fuculose using a fucose isomerase from Raoultella sp. and the biochemical and structural analyses of the enzyme In Jung Kim1†, Do Hyoung Kim1†, Ki Hyun Nam1,2 and Kyoung Heon Kim1* Abstract Background: L-Fucose is a rare sugar with potential uses in the pharmaceutical, cosmetic, and food industries. The enzymatic approach using L-fucose isomerase, which interconverts L-fucose and L-fuculose, can be an efcient way of producing L-fucose for industrial applications. Here, we performed biochemical and structural analyses of L-fucose isomerase identifed from a novel species of Raoultella (RdFucI). Results: RdFucI exhibited higher enzymatic activity for L-fuculose than for L-fucose, and the rate for the reverse reaction of converting L-fuculose to L-fucose was higher than that for the forward reaction of converting L-fucose to L-fuculose. In the equilibrium mixture, a much higher proportion of L-fucose (~ ninefold) was achieved at 30 °C and pH 7, indicating that the enzyme-catalyzed reaction favors the formation of L-fucose from L-fuculose. When biochemical analysis was conducted using L-fuculose as the substrate, the optimal conditions for RdFucI activity were determined to be 40 °C and pH 10. However, the equilibrium composition was not afected by reaction temperature in the range 2 of 30 to 50 °C. Furthermore, RdFucI was found to be a metalloenzyme requiring Mn + as a cofactor. The comparative crystal structural analysis of RdFucI revealed the distinct conformation of α7–α8 loop of RdFucI.
    [Show full text]
  • ( 12 ) United States Patent ( 10 ) Patent No .: US 11,019,776 B2 Klessig Et Al
    US011019776B2 ( 12 ) United States Patent ( 10 ) Patent No .: US 11,019,776 B2 Klessig et al . ( 45 ) Date of Patent : * Jun . 1 , 2021 ( 54 ) COMPOSITIONS AND METHODS FOR AOIN 43/38 ( 2006.01 ) MODULATING IMMUNITY IN PLANTS AOIN 63/10 ( 2020.01 ) ( 52 ) U.S. CI . ( 71 ) Applicant: Boyce Thompson Institute for Plant CPC A01H 3/04 ( 2013.01 ) ; A01N 43/16 Research , Inc. , Ithaca , NY ( US ) ( 2013.01 ) ; AOIN 43/38 ( 2013.01 ) ; AOIN 63/10 ( 2020.01 ) ; C12N 15/8281 ( 2013.01 ) ; ( 72 ) Inventors : Daniel Klessig , Dryden , NY ( US ) ; C12N 15/8282 ( 2013.01 ) ; C12N 15/8283 Frank Schroeder , Ithaca , NY ( US ) ; ( 2013.01 ) ; C12N 15/8285 ( 2013.01 ) Patricia Manosalva, Ithaca, NY ( US ) ( 58 ) Field of Classification Search CPC C12N 15/8282 ; C12N 15/8281 ( 73 ) Assignee : BOYCE THOMPSON INSTITUTE See application file for complete search history. FOR PLANT RESEARCH , INC . , Ithaca , NY (US ) ( 56 ) References Cited ( * ) Notice: Subject to any disclaimer , the term of this U.S. PATENT DOCUMENTS patent is extended or adjusted under 35 U.S.C. 154 ( b ) by 26 days. 8,318,146 B1 11/2012 Teal et al . This patent is subject to a terminal dis FOREIGN PATENT DOCUMENTS claimer . WO 2010/009241 A2 1/2010 WO 2010/146062 A2 12/2010 ( 21 ) Appl. No .: 16 / 161,252 WO 2012/084858 A2 6/2012 WO 2013/022985 A2 2/2013 ( 22 ) Filed : Oct. 16 , 2018 WO 2013/022997 A2 2/2013 ( Continued ) ( 65 ) Prior Publication Data US 2019/0053451 A1 Feb. 21 , 2019 OTHER PUBLICATIONS Hsueh , Y.-P. et al 2013.
    [Show full text]
  • Efficient Enzymatic Synthesis of L-Rhamnulose and L-Fuculose
    Bioorganic & Medicinal Chemistry Letters 26 (2016) 969–972 Contents lists available at ScienceDirect Bioorganic & Medicinal Chemistry Letters journal homepage: www.elsevier.com/locate/bmcl Efficient enzymatic synthesis of L-rhamnulose and L-fuculose y y ⇑ ⇑ Liuqing Wen a, , Lanlan Zang b, , Kenneth Huang a, Shanshan Li a, Runling Wang b, , Peng George Wang a, a Department of Chemistry and Center for Therapeutics and Diagnostics, Georgia State University, Atlanta, GA 30303, USA b Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China article info abstract Article history: L-Rhamnulose (6-deoxy-L-arabino-2-hexulose) and L-fuculose (6-deoxy-L-lyxo-2-hexulose) were prepared Received 2 November 2015 from L-rhamnose and L-fucose by a two-step strategy. In the first reaction step, isomerization of L-rham- Revised 12 December 2015 nose to L-rhamnulose, or L-fucose to L-fuculose was combined with a targeted phosphorylation reaction Accepted 15 December 2015 catalyzed by L-rhamnulose kinase (RhaB). The by-products (ATP and ADP) were selectively removed by Available online 17 December 2015 silver nitrate precipitation method. In the second step, the phosphate group was hydrolyzed to produce L-rhamnulose or L-fuculose with purity exceeding 99% in more than 80% yield (gram scale). Keywords: Ó 2015 Elsevier Ltd. All rights reserved. L-Rhamnulose L-Fuculose Enzymatic synthesis Phosphorylation De-phosphorylation Among 36 hexoses and pentoses (12 ketoses and 24 corre- (RhaD) or L-fuculose 1-phosphate aldolase (FucA) to facilitate fur- sponding aldoses), only seven monosaccharides are naturally ther metabolic function.11 RhaD and FucA are two powerful biocat- present in substantial quantities (D-xylose, D-ribose, L-arabinose, alysts and have been widely used in synthetic chemistry to 1 12 D-galactose, D-glucose, D-mannose, and D-fructose).
    [Show full text]
  • Evolving a New Efficient Mode of Fructose Utilization For
    fbioe-09-669093 May 22, 2021 Time: 22:55 # 1 ORIGINAL RESEARCH published: 28 May 2021 doi: 10.3389/fbioe.2021.669093 Evolving a New Efficient Mode of Fructose Utilization for Improved Bioproduction in Corynebacterium glutamicum Irene Krahn1, Daniel Bonder2, Lucía Torregrosa-Barragán2, Dominik Stoppel1, 1 3 1 3,4 Edited by: Jens P. Krause , Natalie Rosenfeldt , Tobias M. Meiswinkel , Gerd M. Seibold , Pablo Ivan Nikel, Volker F. Wendisch1 and Steffen N. Lindner1,2* Novo Nordisk Foundation Center 1 2 for Biosustainability (DTU Biosustain), Chair of Genetics of Prokaryotes, Faculty of Biology and CeBiTec, Bielefeld University, Bielefeld, Germany, Systems 3 Denmark and Synthetic Metabolism, Max Planck Institute of Molecular Plant Physiology, Potsdam-Golm, Germany, Institute of Biochemistry, University of Cologne, Cologne, Germany, 4 Department of Biotechnology and Biomedicine, Technical Reviewed by: University of Denmark, Lyngby, Denmark Stephan Noack, Julich-Forschungszentrum, Helmholtz-Verband Deutscher Fructose utilization in Corynebacterium glutamicum starts with its uptake and Forschungszentren (HZ), Germany concomitant phosphorylation via the phosphotransferase system (PTS) to yield Fabien Létisse, UMR 5504 Laboratoire d’Ingénierie intracellular fructose 1-phosphate, which enters glycolysis upon ATP-dependent des Systèmes Biologiques et des phosphorylation to fructose 1,6-bisphosphate by 1-phosphofructokinase. This is known Procédés (LISBP), France to result in a significantly reduced oxidative pentose phosphate pathway (oxPPP) flux *Correspondence: ∼ ∼ Steffen N. Lindner on fructose ( 10%) compared to glucose ( 60%). Consequently, the biosynthesis of [email protected] NADPH demanding products, e.g., L-lysine, by C. glutamicum is largely decreased when fructose is the only carbon source. Previous works reported that fructose Specialty section: This article was submitted to is partially utilized via the glucose-specific PTS presumably generating fructose 6- Synthetic Biology, phosphate.
    [Show full text]
  • Estimation of Free Methylpentoses in the Presence of Glycosidically Bound Sugar1
    ANALYTICAL BIOCHEMISTRY 14, 278-289 (1966) Estimation of Free Methylpentoses in the Presence of Glycosidically Bound Sugar1 A. K. BHATTACHARYYA AND D. AMINOFF From the Simpson Memorial Institute, The University of Michigan, Ann Arbor, Michigan Received August 3, 1965 In the course of our investigations on the immunochemistry and bio- synthesis of the human blood group substances, it became necessary to determine the amount of free fucose in the presence of the glycosidically bound sugar. Dische and Shettles (1) have described a specific spectro- photometric procedure for the determination of methylpentoses. This involved heating with concentrated sulfuric acid and the development of a specific color with cysteine hydrochloride. Modifications of the method have been described (2, 3) but in each case a strong acid is employed in the reagent. The heating with the acidic reagents releases methyl- pentose and converts it to the appropriate chromogen. Thus, these methods do not distinguish between free and bound methylpentoses. In- direct methods were therefore used to determine the rate of release of methylpentose under varying conditions of hydrolysis. One such method involved chromatographic separation of the sugars in the hydrolysis products followed by quantitative determination of the area correspond- ing to free fucose either by the cysteine-H&SO4 method (1) or by the Somogyi-Nelson procedure (4). Recovery of methylpentoses by these techniques was invariably low. This paper describes a procedure which involves the oxidation of methylpentoses with periodate. Only the free methylpentose will release acetaldehyde on oxidation with periodate and thus can be determined in the presence of the glycosidically bound compound.
    [Show full text]
  • Expanding the Reaction Space of Aldolases Using Hydroxypyruvate As Nucleophile Substrate
    Electronic Supplementary Material (ESI) for Green Chemistry. This journal is © The Royal Society of Chemistry 2016 Expanding the reaction space of aldolases using hydroxypyruvate as nucleophile substrate Supporting Information Véronique de Berardinis,a Christine Guérard-Hélaine,b Ekaterina Darii,a Karine Bastard,a Virgil Hélaine,b Aline Mariage,a Jean-Louis Petit,a Nicolas Poupard,b Israel Sanchez-Moreno,b Mark Stam,a Thierry Gefflaut,b Marcel Salanoubat,a and Marielle Lemaireb a Commissariat à l’Energie Atomique et aux énergies alternatives, Direction de la Recherche Fondamentale, Institut de Génomique, Genoscope, UMR 8030, 91057 Evry, France ; Université d’Evry Val d’Essonne, UMR 8030, 91057 Evry, France ; Centre National de la Recherche Scientifique, UMR8030, 91057 Evry, France b Clermont Université, Université Blaise Pascal, ICCF, BP 10448, F-63000 Clermont-Ferrand, France ; CNRS, UMR 6296, BP 80026, F-63177 Aubière, France. 1. Materials ...............................................................................................................................................................................2 2. Methods ................................................................................................................................................................................2 2.1. Method S1. Set up of the candidate collection to be screened..................................................................................2 2.2. Method S2. Cloning, expression and cell free extract preparation. ..........................................................................2
    [Show full text]
  • The Quest for Novel Extracellular Polymers Produced by Soil-Borne Bacteria
    Copyright is owned by the Author of the thesis. Permission is given for a copy to be downloaded by an individual for the purpose of research and private study only. The thesis may not be reproduced elsewhere without the permission of the Author. Bioprospecting: The quest for novel extracellular polymers produced by soil-borne bacteria A thesis presented in partial fulfilment of the requirements for the degree of Master of Science In Microbiology at Massey University, Palmerston North, New Zealand Jason Smith 2017 i Dedication This thesis is dedicated to my dad. Vaughan Peter Francis Smith 13 July 1955 – 27 April 2002 Though our time together was short you are never far from my mind nor my heart. ii Abstract Bacteria are ubiquitous in nature, and the surrounding environment. Bacterially produced extracellular polymers, and proteins are of particular value in the fields of medicine, food, science, and industry. Soil is an extremely rich source of bacteria with over 100 million per gram of soil, many of which produce extracellular polymers. Approximately 90% of soil-borne bacteria are yet to be cultured and classified. Here we employed an exploratory approach and culture based method for the isolation of soil-borne bacteria, and assessed their capability for extracellular polymer production. Bacteria that produced mucoid (of a mucous nature) colonies were selected for identification, imaging, and polymer production. Here we characterised three bacterial isolates that produced extracellular polymers, with a focus on one isolate that formed potentially novel proteinaceous cell surface appendages. These appendages have an unknown function, however, I suggest they may be important for bacterial communication, signalling, and nutrient transfer.
    [Show full text]
  • Chemoenzymatic Synthesis of Sugar-Related Polyhydroxylated Compounds, Iminocyclitols and Their Derivatives As Glycosidase Inhibitors
    Chemoenzymatic synthesis of sugar-related polyhydroxylated compounds, iminocyclitols and their derivatives as glycosidase inhibitors Alda Lisa Concia ADVERTIMENT. La consulta d’aquesta tesi queda condicionada a l’acceptació de les següents condicions d'ús: La difusió d’aquesta tesi per mitjà del servei TDX (www.tdx.cat) i a través del Dipòsit Digital de la UB (diposit.ub.edu) ha estat autoritzada pels titulars dels drets de propietat intel·lectual únicament per a usos privats emmarcats en activitats d’investigació i docència. No s’autoritza la seva reproducció amb finalitats de lucre ni la seva difusió i posada a disposició des d’un lloc aliè al servei TDX ni al Dipòsit Digital de la UB. No s’autoritza la presentació del seu contingut en una finestra o marc aliè a TDX o al Dipòsit Digital de la UB (framing). Aquesta reserva de drets afecta tant al resum de presentació de la tesi com als seus continguts. En la utilització o cita de parts de la tesi és obligat indicar el nom de la persona autora. ADVERTENCIA. La consulta de esta tesis queda condicionada a la aceptación de las siguientes condiciones de uso: La difusión de esta tesis por medio del servicio TDR (www.tdx.cat) y a través del Repositorio Digital de la UB (diposit.ub.edu) ha sido autorizada por los titulares de los derechos de propiedad intelectual únicamente para usos privados enmarcados en actividades de investigación y docencia. No se autoriza su reproducción con finalidades de lucro ni su difusión y puesta a disposición desde un sitio ajeno al servicio TDR o al Repositorio Digital de la UB.
    [Show full text]
  • Biotechnological Production of Glycolic Acid and Ethylene Glycol: Current State and Perspectives
    Applied Microbiology and Biotechnology https://doi.org/10.1007/s00253-019-09640-2 MINI-REVIEW Biotechnological production of glycolic acid and ethylene glycol: current state and perspectives Laura Salusjärvi1 & Sami Havukainen1 & Outi Koivistoinen1 & Mervi Toivari1 Received: 4 September 2018 /Revised: 8 January 2019 /Accepted: 9 January 2019 # The Author(s) 2019 Abstract Glycolic acid (GA) and ethylene glycol (EG) are versatile two-carbon organic chemicals used in multiple daily applications. GA and EG are currently produced by chemical synthesis, but their biotechnological production from renewable resources has received a substantial interest. Several different metabolic pathways by using genetically modified microorganisms, such as Escherichia coli, Corynebacterium glutamicum and yeast have been established for their production. As a result, the yield of GA and EG produced from sugars has been significantly improved. Here, we describe the recent advancement in metabolic engi- neering efforts focusing on metabolic pathways and engineering strategies used for GA and EG production. Keywords Glycolic acid . Ethylene glycol . D-xylose . Glyoxylate shunt . D-xylulose-1-phosphate pathway . D-ribulose-1-phosphate pathway . L-xylulose-1-phosphate pathway . Dahms pathway . Serine pathway . Metabolic engineering . Biotechnology . Biorefinery Introduction agents. The market is expected to reach US$415.0 million by 2024 (https://www.grandviewresearch.com/press-release/ Glycolic acid (GA) is a small two-carbon α-hydroxy acid global-glycolic-acid-market). (Fig. 1a) with both alcohol and acid groups (pKa 3.83). GA is naturally produced by some chemolithotrophic iron- Textile industry uses GA as a dyeing and tanning agent, in and sulphur-oxidizing bacteria (Nancucheo and Johnson food industry, it is used as a flavour and preservative and in the 2010) or from glycolonitrile by hydrolyzation by nitrilase en- pharmaceutical industry as a skin care agent.
    [Show full text]
  • Facile Enzymatic Synthesis of Ketoses and Chemoenzymatic Reporter Strategy for Probing Complex Glycans Liuqing Wen
    Georgia State University ScholarWorks @ Georgia State University Chemistry Dissertations Department of Chemistry Spring 5-10-2017 Facile Enzymatic Synthesis of Ketoses and Chemoenzymatic Reporter Strategy for Probing Complex Glycans liuqing Wen Follow this and additional works at: https://scholarworks.gsu.edu/chemistry_diss Recommended Citation Wen, liuqing, "Facile Enzymatic Synthesis of Ketoses and Chemoenzymatic Reporter Strategy for Probing Complex Glycans." Dissertation, Georgia State University, 2017. https://scholarworks.gsu.edu/chemistry_diss/131 This Dissertation is brought to you for free and open access by the Department of Chemistry at ScholarWorks @ Georgia State University. It has been accepted for inclusion in Chemistry Dissertations by an authorized administrator of ScholarWorks @ Georgia State University. For more information, please contact [email protected]. i FACILE ENZYMATIC SYNTHESIS OF KETOSES & CHEMOENZYMATIC REPORTER STRATEGY FOR PROBING COMPLEX GLYCANS by LIUQING WEN Under the Direction of Peng George Wang (PhD) ii ABSTRACT Of all possible ketoses, only D-fructose occur large scale in nature. Therefore, all the ketoses with the exception of D-fructose are defined as “rare ketose”. Despite their lower accessibility, rare ketoses offer an enormous potential for applications in pharmaceutical, medicine, functional food and synthetic chemistry. However, studies of rare ketoses have been hampered by the lack of efficient preparation methods. Here, a convenient and efficient platform for the facile synthesis of rare ketoses is described. The introduced two-step strategies are based on a “phosphorylationde-phosphorylation” cascade reaction. Rare ketoses were prepared from readily available starting materials as their ketose-1-phosphate forms in step 1 by one-pot multienzyme reactions, followed by the hydrolysis of the phosphate groups in acidic conditions to produce desired ketoses in step 2.
    [Show full text]
  • WO 2015/006740 A2 15 January 2015 (15.01.2015) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/006740 A2 15 January 2015 (15.01.2015) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 47/48 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, PCT/US20 14/046425 DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, 11 July 2014 ( 11.07.2014) KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (25) Filing Language: English OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (26) Publication Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (30) Priority Data: ZW. 61/845,279 11 July 2013 ( 11.07.2013) US (84) Designated States (unless otherwise indicated, for every (71) Applicant: ALNYLAM PHARMACEUTICALS, INC. kind of regional protection available): ARIPO (BW, GH, [US/US]; 300 Third Street, Cambridge, MA 02142 (US). GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (72) Inventors: MANOHARAN, Muthiah; 300 Third Street, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, Cambridge, MA 02142 (US).
    [Show full text]
  • Triphosphate Disodium Salt
    Chemily Glycoscience Chemily is a research, development, and consulting company dedicated to advancing Glycoscience. We specialize in carbohydrate-based biochemicals, reagents and pharmaceuticals, and have been manufacturing several categories of products using our proprietary chemo-enzymatic and in vivo bioengineering technology. Our products include: Glyco-related enzymes: glycosyltransferases, glycosidases, sugar nucleotide biosynthesized enzymes Sugar nucleotides and their derivatives Structure-defined oligosaccharides: N-Glycan, HMO, H, L, and TE Carbohydrate-based pharmaceuticals and glycoprotein vaccines * Bulk quantities are available upon request. We also offer a wide range of glycomics and proteomics’ services. We utilize state-of-the-art mass spectrometry instrumentation and workflows to provide protein / glycan analysis. Our team, with years of experience, will provide reliable results to facilitate your research, and we hope to be your first choice when you are seeking a partner to accelerate your projects. Our services include: Protein identification (Protein ID) Global proteomic profiling Global profiling of N-linked glycosylation sites Global glycomic profiling Glycoprotein analysis We look forward to working with you on your future research needs! 58 Edgewood Ave. www.chemilyglycoscience.com Atlanta, GA, 30303 [email protected] United States Tel: +1-(404)413-3557 Glycoenzymes Glycosyltransferases (GTs) The majority of GTs are Leloir-type enzymes, and utilize nucleotide sugars as their substrate for adding sugar residues to substrate glycoproteins and growing polysaccharides. While nucleotide sugars are locked in their anomeric state, GTs will either retain or invert the anomeric configuration of the sugar, depending on the mechanism of the transferase reaction it employs. For example, an inverting GT will add UDP-α-D- glucuronic acid to a substrate, forming a 훽 glycosidic linkage.
    [Show full text]