Abstract
As one of the most basic molecules that constitute a living body, saccharides not only play the role of energy storage and have many important biological functions that are constantly revealed and recognized. Generally, a glycoside composed of 2–10 monosaccharides linked together by a glycosidic bond belongs to oligosaccharide, and a glycoside composed of 10 or more monosaccharides belongs to polysaccharide. Usually, the number of monosaccharides in the polysaccharide exceeds 100, and the molecular weight can reach tens of thousands or even millions Da. Oligosaccharides and polysaccharides have attracted widespread attention in a variety of applications in cosmetics, health care products (such as immunomodulation, protection of the knee and liver), and various disease treatments (such as anti-tumor, anti-viral, and hypoglycemic). However, at present, most of the oligosaccharides and polysaccharides are still extracted from animal tissues, which have problems such as unstable source of raw materials, potential allergens and contaminants. As a result, more and more oligosaccharides and polysaccharides have been tried to use microbial production, many of which have even entered the stage of large-scale industrial production. This chapter mainly introduces the metabolic engineering and synthetic biology strategies of microbial production of oligosaccharides and polysaccharides through several typical products, including hyaluronic acid, glucosamine/N-acetylglucosamine, heparin, chondroitin sulfate, human milk oligosaccharides, xanthan gum and chitin oligosaccharides.
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References
Barreteau H, Richard E, Drouillard S, Samain E, Priem B. Production of intracellular heparosan and derived oligosaccharides by lyase expression in metabolically engineered E. coli K-12. Carbohydr Res. 2012;360:19–24. https://doi.org/10.1016/j.carres.2012.07.013.
Becker DJ, Lowe JB. Biosynthesis and biological function in mammals. Glycobiology. 2003;13:41R–53R. https://doi.org/10.1093/glycob/cwg054.
Benhabiles MS, et al. Antibacterial activity of chitin, chitosan and its oligomers prepared from shrimp shell waste. Food Hydrocoll. 2012;29:48–56. https://doi.org/10.1016/j.foodhyd.2012.02.013.
Blazeck J, Alper H. Systems metabolic engineering. Genome-scale models and beyond. Biotechnol J. 2010;5:647–59. https://doi.org/10.1002/biot.200900247.
Bode L. Human milk oligosaccharides. Every baby needs a sugar mama. Glycobiology. 2012;22:1147–62. https://doi.org/10.1093/glycob/cws074.
Bode L. The functional biology of human milk oligosaccharides. Early Hum Dev. 2015;91:619–22. https://doi.org/10.1016/j.earlhumdev.2015.09.001.
Bode L, et al. Overcoming the limited availability of human milk oligosaccharides. Challenges and opportunities for research and application. Nutr Rev. 2016;74:635–44. https://doi.org/10.1093/nutrit/nuw025.
Boltje TJ, Buskas T, Boons G-J. Opportunities and challenges in synthetic oligosaccharide and glycoconjugate research. Nat Chem. 2009;1:611–22. https://doi.org/10.1038/nchem.399.
Bych K, et al. Production of HMOs using microbial hosts — from cell engineering to large scale production. Curr Opin Biotechnol. 2019;56:130–7. https://doi.org/10.1016/j.copbio.2018.11.003.
Casas J, Santos V, Garcı́a-Ochoa F. Xanthan gum production under several operational conditions. Molecular structure and rheological properties☆. Enzyme Microb Technol. 2000;26:282–91. https://doi.org/10.1016/S0141-0229(99)00160-X.
Chavaroche AA, van den Broek LAM, Eggink G. Production methods for heparosan, a precursor of heparin and heparan sulfate. Carbohydr Polym. 2013;93:38–47. https://doi.org/10.1016/j.carbpol.2012.04.046.
Chen J-K, Shen C-R, Liu C-L. N-acetylglucosamine. Production and applications. Mar Drugs. 2010;8:2493–516. https://doi.org/10.3390/md8092493.
Chin Y-W, Kim J-Y, Lee W-H, Seo J-H. Enhanced production of 2′-fucosyllactose in engineered Escherichia coli BL21star(DE3) by modulation of lactose metabolism and fucosyltransferase. J Biotechnol. 2015;210:107–15. https://doi.org/10.1016/j.jbiotec.2015.06.431.
Chin Y-W, Seo N, Kim J-H, Seo J-H. Metabolic engineering of Escherichia coli to produce 2′-fucosyllactose via salvage pathway of guanosine 5′-diphosphate (GDP)-l-fucose. Biotechnol Bioeng. 2016;113:2443–52. https://doi.org/10.1002/bit.26015.
Chong BF, Blank LM, Mclaughlin R, Nielsen LK. Microbial hyaluronic acid production. Appl Microbiol Biotechnol. 2005;66:341–51. https://doi.org/10.1007/s00253-004-1774-4.
Cimini D, Restaino OF, Catapano A, De Rosa M, Schiraldi C. Production of capsular polysaccharide from Escherichia coli K4 for biotechnological applications. Appl Microbiol Biotechnol. 2010a;85:1779–87. https://doi.org/10.1007/s00253-009-2261-8.
Cimini D, et al. Improved fructosylated chondroitin production by kfoC overexpression in E. coli K4. J Biotechnol. 2010b;150:324–31. https://doi.org/10.1016/j.jbiotec.2010.09.954.
Cimini D, De Rosa M, Carlino E, Ruggiero A, Schiraldi C. Homologous overexpression of rfaH in E. coli K4 improves the production of chondroitin-like capsular polysaccharide. Microb Cell Fact. 2013;12:46. https://doi.org/10.1186/1475-2859-12-46.
Cziraky MJ, Spinler SA. Low-molecular-weight heparins for the treatment of deep-vein thrombosis. Clin Pharm. 1993;12:892–9.
Deangelis PL. Evolution of glycosaminoglycans and their glycosyltransferases. Implications for the extracellular matrices of animals and the capsules of pathogenic bacteria. Anat Rec. 2002;268:317–26. https://doi.org/10.1002/ar.10163.
Deangelis PL. Glycosaminoglycan polysaccharide biosynthesis and production. Today and tomorrow. Appl Microbiol Biotechnol. 2012;94:295–305. https://doi.org/10.1007/s00253-011-3801-6.
Deangelis PL, White CL. Identification and molecular cloning of a heparosan synthase from Pasteurella multocida type D. J Biol Chem. 2002;277:7209–13. https://doi.org/10.1074/jbc.M112130200.
Dickendesher TL, et al. NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans. Nat Neurosci. 2012;15:703 EP. https://doi.org/10.1038/nn.3070.
Dostrovsky NR, Towheed TE, Hudson RW, Anastassiades TP. The effect of glucosamine on glucose metabolism in humans. A systematic review of the literature. Osteoarthr Cartil. 2011;19:375–80. https://doi.org/10.1016/j.joca.2011.01.007.
Dumon C, et al. In vivo fucosylation of lacto-N-neotetraose and lacto-N-neohexaose by heterologous expression of Helicobacter pylori α-1,3 fucosyltransferase in engineered Escherichia coli. Glycoconj J. 2001;18:465–74. https://doi.org/10.1023/A:1016086118274.
Elison E, et al. Oral supplementation of healthy adults with 2′-O-fucosyllactose and lacto-N-neotetraose is well tolerated and shifts the intestinal microbiota. Br J Nutr. 2016;116:1356–68. https://doi.org/10.1017/S0007114516003354.
Elshahawi SI, Shaaban KA, Kharel MK, Thorson JS. A comprehensive review of glycosylated bacterial natural products. Chem Soc Rev. 2015;44:7591–697. https://doi.org/10.1039/c4cs00426d.
Engels L, Elling L. WbgL. A novel bacterial α1,2-fucosyltransferase for the synthesis of 2′-fucosyllactose. Glycobiology. 2013;24:170–8. https://doi.org/10.1093/glycob/cwt096.
Fareed J, Bacher P, Jeske W. Advances in heparins and related research. An epilogue. Molecules. 2018;23:pii: E390. https://doi.org/10.3390/molecules23020390.
Faria S, Vieira PA, Resende MM, Ribeiro EJ, Cardoso VL. Application of a model using the phenomenological approach for prediction of growth and xanthan gum production with sugar cane broth in a batch process. LWT- Food Sci Technol. 2010;43:498–506. https://doi.org/10.1016/j.lwt.2009.09.018.
Fernandes JC, et al. Antimicrobial effects of chitosans and chitooligosaccharides, upon Staphylococcus aureus and Escherichia coli, in food model systems. Food Microbiol. 2008;25:922–8. https://doi.org/10.1016/j.fm.2008.05.003.
Fernandes JC, et al. Anti-inflammatory activity of chitooligosaccharides in vivo. Mar Drugs. 2010;8:1763–8. https://doi.org/10.3390/md8061763.
Fujikawa S-i, Ohmae M, Kobayashi S. Enzymatic synthesis of chondroitin 4-sulfate with well-defined structure. Biomacromolecules. 2005;6:2935–42. https://doi.org/10.1021/bm050364p.
Gu Y, et al. Rewiring the glucose transportation and central metabolic pathways for overproduction of N-acetylglucosamine in Bacillus subtilis. Biotechnol J. 2017;12:1700020. https://doi.org/10.1002/biot.201700020.
Gu Y, et al. Synthetic redesign of central carbon and redox metabolism for high yield production of N-acetylglucosamine in Bacillus subtilis. Metab Eng. 2019;51:59–69. https://doi.org/10.1016/j.ymben.2018.10.002.
Guerrini M, et al. Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events. Nat Biotechnol. 2008;26:669–75. https://doi.org/10.1038/nbt1407.
Guiziou S, et al. A part toolbox to tune genetic expression in Bacillus subtilis. Nucleic Acids Res. 2016;44:7495–508. https://doi.org/10.1093/nar/gkw624.
Hänfling P, Shashkov AS, Jann B, Jann K. Analysis of the enzymatic cleavage (beta elimination) of the capsular K5 polysaccharide of Escherichia coli by the K5-specific coliphage. Reexamination. J Bacteriol. 1996;178:4747–50. https://doi.org/10.1128/jb.178.15.4747-4750.1996.
He W, et al. Production of chondroitin in metabolically engineered E. coli. Metab Eng. 2015;27:92–100. https://doi.org/10.1016/j.ymben.2014.11.003.
Hemker HC. A century of heparin. Past, present and future. J Thromb Haemost. 2016;14:2329–38. https://doi.org/10.1111/jth.13555.
Huang R, Mendis E, Rajapakse N, Kim S-K. Strong electronic charge as an important factor for anticancer activity of chitooligosaccharides (COS). Life Sci. 2006;78:2399–408. https://doi.org/10.1016/j.lfs.2005.09.039.
Huang D, et al. Metabolic engineering of Escherichia coli for the production of 2′-fucosyllactose and 3-fucosyllactose through modular pathway enhancement. Metab Eng. 2017;41:23–38. https://doi.org/10.1016/j.ymben.2017.03.001.
Jin P, et al. Efficient biosynthesis of polysaccharides chondroitin and heparosan by metabolically engineered Bacillus subtilis. Carbohydr Polym. 2016a;140:424–32. https://doi.org/10.1016/j.carbpol.2015.12.065.
Jin P, Kang Z, Yuan P, Du G, Chen J. Production of specific-molecular-weight hyaluronan by metabolically engineered Bacillus subtilis 168. Metab Eng. 2016b;35:21–30. https://doi.org/10.1016/j.ymben.2016.01.008.
Jung W-J, Park R-D. Bioproduction of chitooligosaccharides. Present and perspectives. Mar Drugs. 2014;12:5328–56. https://doi.org/10.3390/md12115328.
Kang Z, et al. Bio-based strategies for producing glycosaminoglycans and their oligosaccharides. Trends Biotechnol. 2018;36:806–18. https://doi.org/10.1016/j.tibtech.2018.03.010.
Kennedy J. Herb and supplement use in the US adult population. Clin Ther. 2005;27:1847–58. https://doi.org/10.1016/j.clinthera.2005.11.004.
Kobayashi S, Fujikawa S-i, Ohmae M. Enzymatic synthesis of chondroitin and its derivatives catalyzed by hyaluronidase. J Am Chem Soc. 2003;125:14357–69. https://doi.org/10.1021/ja036584x.
Kubomura D, Ueno T, Yamada M, Nagaoka I. Evaluation of the chondroprotective action of N-acetylglucosamine in a rat experimental osteoarthritis model. Exp Ther Med. 2017;14:3137–44. https://doi.org/10.3892/etm.2017.4849.
Kumar A, Rao KM, Han SS. Application of xanthan gum as polysaccharide in tissue engineering. A review. Carbohydr Polym. 2018;180:128–44. https://doi.org/10.1016/j.carbpol.2017.10.009.
Kunz C. Historical aspects of human milk oligosaccharides. Adv Nutr (Bethesda, Md). 2012;3:430S–9S. https://doi.org/10.3945/an.111.001776.
Laremore TN, Zhang F, Dordick JS, Liu J, Linhardt RJ. Recent progress and applications in glycosaminoglycan and heparin research. Curr Opin Chem Biol. 2009;13:633–40. https://doi.org/10.1016/j.cbpa.2009.08.017.
Lee W-H, Han N-S, Park Y-C, Seo J-H. Modulation of guanosine 5′-diphosphate-d-mannose metabolism in recombinant Escherichia coli for production of guanosine 5′-diphosphate-l-fucose. Bioresour Technol. 2009;100:6143–8. https://doi.org/10.1016/j.biortech.2009.07.035.
Lee W-H, Chin Y-W, Han NS, Kim M-D, Seo J-H. Enhanced production of GDP-L-fucose by overexpression of NADPH regenerator in recombinant Escherichia coli. Appl Microbiol Biotechnol. 2011;91:967–76. https://doi.org/10.1007/s00253-011-3271-x.
Lee W-H, Shin S-Y, Kim M-D, Han NS, Seo J-H. Modulation of guanosine nucleotides biosynthetic pathways enhanced GDP-l-fucose production in recombinant Escherichia coli. Appl Microbiol Biotechnol. 2012;93:2327–34. https://doi.org/10.1007/s00253-011-3776-3.
Lidholt K, Riesenfeld J, Jacobsson KG, Feingold DS, Lindahl U. Biosynthesis of heparin. Modulation of polysaccharide chain length in a cell-free system. Biochem J. 1988;254:571–8. https://doi.org/10.1042/bj2540571.
Ling M, et al. Combinatorial promoter engineering of glucokinase and phosphoglucoisomerase for improved N-acetylglucosamine production in Bacillus subtilis. Bioresour Technol. 2017;245:1093–102. https://doi.org/10.1016/j.biortech.2017.09.063.
Ling M, Li J, Du G, Liu L. Metabolic engineering for the production of chitooligosaccharides. Advances and perspectives. Emerg Top Life Sci. 2018;2:377. https://doi.org/10.1042/ETLS20180009.
Linhardt RJ. 2003 Claude S. Hudson Award address in carbohydrate chemistry. Heparin: structure and activity. J Med Chem. 2003;46:2551–64. https://doi.org/10.1021/jm030176m.
Liu H, Zhang Z, Linhardt RJ. Lessons learned from the contamination of heparin. Nat Prod Rep. 2009a;26:313–21. https://doi.org/10.1039/b819896a.
Liu L, Sun J, Xu W, Du G, Chen J. Modeling and optimization of microbial hyaluronic acid production by Streptococcus zooepidemicus using radial basis function neural network coupling quantum-behaved particle swarm optimization algorithm. Biotechnol Prog. 2009b;25:1819–25. https://doi.org/10.1002/btpr.278.
Liu L, Liu Y, Li J, Du G, Chen J. Microbial production of hyaluronic acid. Current state, challenges, and perspectives. Microb Cell Fact. 2011;10:99. https://doi.org/10.1186/1475-2859-10-99.
Liu L, et al. Microbial production of glucosamine and N-acetylglucosamine. Advances and perspectives. Appl Microbiol Biotechnol. 2013a;97:6149–58. https://doi.org/10.1007/s00253-013-4995-6.
Liu Y, et al. Pathway engineering of Bacillus subtilis for microbial production of N-acetylglucosamine. Metab Eng. 2013b;19:107–15. https://doi.org/10.1016/j.ymben.2013.07.002.
Liu Y, et al. Spatial modulation of key pathway enzymes by DNA-guided scaffold system and respiration chain engineering for improved N-acetylglucosamine production by Bacillus subtilis. Metab Eng. 2014a;24:61–9. https://doi.org/10.1016/j.ymben.2014.04.004.
Liu Y, et al. Modular pathway engineering of Bacillus subtilis for improved N-acetylglucosamine production. Metab Eng. 2014b;23:42–52. https://doi.org/10.1016/j.ymben.2014.02.005.
Liu Y, et al. A dynamic pathway analysis approach reveals a limiting futile cycle in N-acetylglucosamine overproducing Bacillus subtilis. Nat Commun. 2016;7:11933. https://doi.org/10.1038/ncomms11933.
Ma W, et al. Metabolic engineering of carbon overflow metabolism of Bacillus subtilis for improved N-acetyl-glucosamine production. Bioresour Technol. 2018;250:642–9. https://doi.org/10.1016/j.biortech.2017.10.007.
Ma W, et al. Combinatorial fine-tuning of GNA1 and GlmS expression by 5′-terminus fusion engineering leads to overproduction of N-Acetylglucosamine in Bacillus subtilis. Biotechnol J. 2019;14:1800264. https://doi.org/10.1002/biot.201800264.
Ma W, et al. Combinatorial pathway enzyme engineering and host engineering overcomes pyruvate overflow and enhances overproduction of N-acetylglucosamine in Bacillus subtilis. Microb Cell Fact. 2019;18(1). https://doi.org/10.1186/s12934-018-1049-x.
Manzoni M, Bergomi S, Molinari F, Cavazzoni V. Production and purification of an extracellularly produced K4 polysaccharide from Escherichia coli. Biotechnol Lett. 1996;18:383–6. https://doi.org/10.1007/BF00143456.
McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis a systematic quality assessment and meta-analysis. JAMA. 2000;283:1469–75. https://doi.org/10.1001/jama.283.11.1469.
Mende M, et al. Chemical synthesis of glycosaminoglycans. Chem Rev. 2016;116:8193–255. https://doi.org/10.1021/acs.chemrev.6b00010.
Mittal H, Kumar V, Saruchi, Ray SS. Adsorption of methyl violet from aqueous solution using gum xanthan/Fe3O4 based nanocomposite hydrogel. Int J Biol Macromol. 2016;89:1–11. https://doi.org/10.1016/j.ijbiomac.2016.04.050.
Nakamura H. Application of glucosamine on human disease—osteoarthritis. Carbohydr Polym. 2011;84:835–9. https://doi.org/10.1016/j.carbpol.2010.08.078.
Niu T, et al. Engineering a glucosamine-6-phosphate responsive glmS ribozyme switch enables dynamic control of metabolic flux in Bacillus subtilis for overproduction of N-Acetylglucosamine. ACS Synth Biol. 2018;7:2423–35. https://doi.org/10.1021/acssynbio.8b00196.
Onishi A, St Ange K, Dordick JS, Linhardt RJ. Heparin and anticoagulation. Front Biosci (Landmark Ed). 2016;21:1372–92.
Palaniraj A, Jayaraman V. Production, recovery and applications of xanthan gum by Xanthomonas campestris. J Food Eng. 2011;106:1–12. https://doi.org/10.1016/j.jfoodeng.2011.03.035.
Pavelká K, et al. Glucosamine sulfate use and delay of progression of knee osteoarthritis. A 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med. 2002;162:2113–23. https://doi.org/10.1001/archinte.162.18.2113.
Prudden AR, et al. Synthesis of asymmetrical multiantennary human milk oligosaccharides. Proc Natl Acad Sci. 2017;114:6954. https://doi.org/10.1073/pnas.1701785114.
Puccio G, et al. Effects of infant formula with human milk oligosaccharides on growth and morbidity. A randomized multicenter trial. J Pediatr Gastroenterol Nutr. 2017;64:624–31. https://doi.org/10.1097/MPG.0000000000001520.
Quinlan AV. Kinetics of secondary metabolite synthesis in batch culture when two different substrates limit cell growth and metabolite production. Xanthan synthesis by Xanthomonas campestrisa. Ann N Y Acad Sci. 1986;469:259–69. https://doi.org/10.1111/j.1749-6632.1986.tb26503.x.
Rabenstein DL. Heparin and heparan sulfate. Structure and function. Nat Prod Rep. 2002;19:312–31.
Rainsford KD. Importance of pharmaceutical composition and evidence from clinical trials and pharmacological studies in determining effectiveness of chondroitin sulphate and other glycosaminoglycans. A critique. J Pharm Pharmacol. 2009;61:1263–70. https://doi.org/10.1211/jpp.61.10.0001.
Restaino OF, Di Lauro I, Di Nuzzo R, De Rosa M, Schiraldi C. New insight into chondroitin and heparosan-like capsular polysaccharide synthesis by profiling of the nucleotide sugar precursors. Biosci Rep. 2017;37:BSR20160548. https://doi.org/10.1042/BSR20160548.
Roman E, Roberts I, Lidholt K, Kusche-Gullberg M. Overexpression of UDP-glucose dehydrogenase in Escherichia coli results in decreased biosynthesis of K5 polysaccharide. Biochem J. 2003;374:767–72. https://doi.org/10.1042/BJ20030365.
Rosalam S, England R. Review of xanthan gum production from unmodified starches by Xanthomonas comprestris sp. Enzyme Microb Technol. 2006;39:197–207. https://doi.org/10.1016/j.enzmictec.2005.10.019.
Samain E, Drouillard S, Heyraud A, Driguez H, Geremia RA. Gram-scale synthesis of recombinant chitooligosaccharides in Escherichia coli. Carbohydr Res. 1997;302:35–42. https://doi.org/10.1016/S0008-6215(97)00107-9.
Sandercock PA, Leong TS. Low-molecular-weight heparins or heparinoids versus standard unfractionated heparin for acute ischaemic stroke. Cochrane Database Syst Rev. 2017;4:CD000119. https://doi.org/10.1002/14651858.CD000119.pub4.
Sarnaik A, et al. Metabolic engineering of cyanobacteria for photoautotrophic production of heparosan, a pharmaceutical precursor of heparin. Algal Res. 2019;37:57–63. https://doi.org/10.1016/j.algal.2018.11.010.
Schumann W. Production of recombinant proteins in Bacillus subtilis. Adv Appl Microbiol. 2007;62:137–89.
Shao J, Li M, Jia Q, Lu Y, Wang PG. Sequence of Escherichia coli O128 antigen biosynthesis cluster and functional identification of an α-1,2-fucosyltransferase. FEBS Lett. 2003;553:99–103. https://doi.org/10.1016/S0014-5793(03)00980-3.
Shi L. Bioactivities, isolation and purification methods of polysaccharides from natural products. A review. Int J Biol Macromol. 2016;92:37–48. https://doi.org/10.1016/j.ijbiomac.2016.06.100.
Shi Y-g, et al. Chondroitin sulfate. Extraction, purification, microbial and chemical synthesis. J Chem Technol Biotechnol. 2014;89:1445–65. https://doi.org/10.1002/jctb.4454.
Sitanggang AB, Wu H-S, Wang SS, Ho Y-C. Effect of pellet size and stimulating factor on the glucosamine production using Aspergillus sp. BCRC 31742. Bioresour Technol. 2010;101:3595–601. https://doi.org/10.1016/j.biortech.2009.12.084.
Stallforth P, Lepenies B, Adibekian A, Seeberger PH. Carbohydrates. A frontier in medicinal chemistry. J Med Chem. 2009;52:5561–77. https://doi.org/10.1021/jm900819p.
Stern R, Asari AA, Sugahara KN. Hyaluronan fragments. An information-rich system. Eur J Cell Biol. 2006;85:699–715. https://doi.org/10.1016/j.ejcb.2006.05.009.
Suflita M, Fu L, He W, Koffas M, Linhardt RJ. Heparin and related polysaccharides. Synthesis using recombinant enzymes and metabolic engineering. Appl Microbiol Biotechnol. 2015;99:7465–79. https://doi.org/10.1007/s00253-015-6821-9.
Toole B, Ghatak S, Misra S. Hyaluronan oligosaccharides as a potential anticancer therapeutic. Curr Pharm Biotechnol. 2008;9:249–52. https://doi.org/10.2174/138920108785161569.
van Dijl J, Hecker M. Bacillus subtilis. From soil bacterium to super-secreting cell factory. Microb Cell Fact. 2013;12:3. https://doi.org/10.1186/1475-2859-12-3.
Vann WF, Schmidt MA, Jann B, Jann K. The structure of the capsular polysaccharide (K5 antigen) of urinary-tract-infective Escherichia coli 010:K5:H4. Eur J Biochem. 1981;116:359–64. https://doi.org/10.1111/j.1432-1033.1981.tb05343.x.
Wang Z, et al. E. coli K5 fermentation and the preparation of heparosan, a bioengineered heparin precursor. Biotechnol Bioeng. 2010;107:964–73. https://doi.org/10.1002/bit.22898.
Wang Z, Dordick JS, Linhardt RJ. Escherichia coli K5 heparosan fermentation and improvement by genetic engineering. Bioeng Bugs. 2011;2:63–7. https://doi.org/10.4161/bbug.2.1.14201.
Wang Z, Wu J, Zhu L, Zhan X. Activation of glycerol metabolism in Xanthomonas campestris by adaptive evolution to produce a high-transparency and low-viscosity xanthan gum from glycerol. Bioresour Technol. 2016;211:390–7. https://doi.org/10.1016/j.biortech.2016.03.096.
Warkentin TE, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med. 1995;332:1330–6. https://doi.org/10.1056/NEJM199505183322003.
Williams A, Linhardt RJ, Koffas MA. Metabolic engineering of capsular polysaccharides. Emerg Top Life Sci. 2018;2:337. https://doi.org/10.1042/ETLS20180003.
Wu Q, et al. Transcriptional engineering of Escherichia coli K4 for fructosylated chondroitin production. Biotechnol Prog. 2013;29:1140–9. https://doi.org/10.1002/btpr.1777.
Wu Y, et al. CRISPRi allows optimal temporal control of N-acetylglucosamine bioproduction by a dynamic coordination of glucose and xylose metabolism in Bacillus subtilis. Metab Eng. 2018;49:232–41. https://doi.org/10.1016/j.ymben.2018.08.012.
Xiao Z, et al. Chemoenzymatic synthesis of a library of human milk oligosaccharides. J Org Chem. 2016;81:5851–65. https://doi.org/10.1021/acs.joc.6b00478.
Xu Q, et al. Chitooligosaccharides protect human embryonic hepatocytes against oxidative stress induced by hydrogen peroxide. Marine Biotechnol. 2010;12:292–8. https://doi.org/10.1007/s10126-009-9222-1.
Zhang J, Ding X, Yang L, Kong Z. A serum-free medium for colony growth and hyaluronic acid production by Streptococcus zooepidemicus NJUST01. Appl Microbiol Biotechnol. 2006;72:168–72. https://doi.org/10.1007/s00253-005-0253-x.
Zhang Z, et al. Solution structures of chemoenzymatically synthesized heparin and its precursors. J Am Chem Soc. 2008;130:12998–3007. https://doi.org/10.1021/ja8026345.
Zhang J, Liu L, Li J, Du G, Chen J. Enhanced glucosamine production by Aspergillus sp. BCRC 31742 based on the time-variant kinetics analysis of dissolved oxygen level. Bioresour Technol. 2012a;111:507–11. https://doi.org/10.1016/j.biortech.2012.02.063.
Zhang C, et al. Metabolic engineering of Escherichia coli BL21 for biosynthesis of heparosan, a bioengineered heparin precursor. Metab Eng. 2012b;14:521–7. https://doi.org/10.1016/j.ymben.2012.06.005.
Zhao C, et al. The one-pot multienzyme (OPME) synthesis of human blood group H antigens and a human milk oligosaccharide (HMOS) with highly active Thermosynechococcus elongatus α1–2-fucosyltransferase. Chem Commun. 2016;52:3899–902. https://doi.org/10.1039/C5CC10646J.
Zhou Z, et al. A microbial–enzymatic strategy for producing chondroitin sulfate glycosaminoglycans. Biotechnol Bioeng. 2018;115:1561–70. https://doi.org/10.1002/bit.26577.
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Tian, R., Liu, Y., Liu, L. (2019). Microbial Production of Oligosaccharides and Polysaccharides. In: Liu, L., Chen, J. (eds) Systems and Synthetic Biotechnology for Production of Nutraceuticals . Springer, Singapore. https://doi.org/10.1007/978-981-15-0446-4_4
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