Advertisement

Applied Microbiology and Biotechnology

, Volume 98, Issue 16, pp 6947–6956 | Cite as

Insight into hyaluronic acid molecular weight control

  • Esteban MarcellinEmail author
  • Jennifer A. Steen
  • Lars K. Nielsen
Mini-Review

Abstract

Hyaluronic acid (HA) is a ubiquitous polysaccharide found in humans, animals, bacteria, algae and molluscs. Simple yet sophisticated, HA demonstrates unique and valuable rheological properties. In solution, HA behaves as a stiffened random coil and the resultant behaviour, even at low concentrations, is far from Newtonian or ‘ideal’. These rheological properties are heavily influenced by molecular weight (MW), so it is not surprising that many of the biological functions of HA are dependent on molecular size. The current billion dollar market for HA continues to grow rapidly, both in gross production and the number of applications for its use. Increasing demand, in conjunction with a reticence to use animal-derived HA, has revitalised the market for HA produced by bacterial fermentation. Although the genes and pathways involved in bacterial production of HA are well characterised, the mechanisms that underlie HA MW control are less well understood. By performing a thorough analysis of the proposed mechanisms of MW control in bacterial fermentation, this mini-review tries to elucidate the challenges and future directions for bacterial HA biosynthesis.

Keywords

Hyaluronic acid Molecular weight control Polysaccharides Streptococcus zooepidemicus 

References

  1. Albertí S, Ashbaugh CD, Wessels MR (1998) Structure of the has operon promoter and regulation of hyaluronic acid capsule expression in group A Streptococcus. Mol Microbiol 28:343–353. doi: 10.1046/j.1365-2958.1998.00800.x
  2. Ali M, Hwang E, Cho IH, Moon MH (2012) Characterization of sodium hyaluronate blends using frit inlet asymmetrical flow field-flow fractionation and multiangle light scattering. Anal Bioanal Chem 402:1269–1276. doi: 10.1007/s00216-011-5531-0 PubMedCrossRefGoogle Scholar
  3. Anzai T, Timoney JF, Kuwamoto Y, Fujita Y, Wada R, Inoue T (1999) In vivo pathogenicity and resistance to phagocytosis of Streptococcus equi strains with different levels of capsule expression. Vet Microbiol 67:277–286PubMedCrossRefGoogle Scholar
  4. Armstrong DC, Johns MR (1997) Culture conditions affect the molecular weight properties of hyaluronic acid produced by Streptococcus zooepidemicus. Appl Environ Microbiol 63:2759PubMedCentralPubMedGoogle Scholar
  5. Armstrong DC, Cooney MJ, Johns MR (1997) Growth and amino acid requirements of hyaluronic-acid-producing Streptococcus zooepidemicus. Appl Microbiol Biotechnol 47:309–312. doi: 10.1007/s002530050932 CrossRefGoogle Scholar
  6. Badle SS, Jayaraman G, Ramachandran KB (2014) Ratio of intracellular precursors concentration and their flux influences hyaluronic acid molecular weight in Streptococcus zooepidemicus and recombinant Lactococcus lactis (Accepted). Bioresour Technol 163C:222–227. doi: 10.1016/j.biortech.2014.04.027 CrossRefGoogle Scholar
  7. Balazs EA (1974) The physical properties of synovial fluid and the special role of hyaluronic acid. In: Helfet A (ed) Disorders of the knee. T.B. Lippincott Company, Philadelphia, pp 63–75Google Scholar
  8. Balazs EA, Leshchiner E (1984) Cross-linked gels of hyaluronic acid and products containing such gels. USA Patent US4582865Google Scholar
  9. Balazs EA, Leshchiner EA, Leshchiner A, Band P (1987) Chemically modified hyaluronic acid preparation and method of recovery thereof from animal tissues. USA Patent US4713448Google Scholar
  10. Blank LM, McLaughlin RL, Nielsen LK (2005) Stable production of hyaluronic acid in Streptococcus zooepidemicus chemostats operated at high dilution rate. Biotechnol Bioeng 90:685–693. doi: 10.1002/Bit.20466 PubMedCrossRefGoogle Scholar
  11. Blank LM, Hugenholtz P, Nielsen LK (2008) Evolution of the hyaluronic acid synthesis (has) operon in Streptococcus zooepidemicus and other pathogenic streptococci. J Mol Evol 67:13–22. doi: 10.1007/s00239-008-9117-1 PubMedCrossRefGoogle Scholar
  12. Bothner H, Waaler T, Wik O (1988) Limiting viscosity number and weight average molecular weight of hyaluronate samples produced by heat degradation. Int J Biol Macromol 10:287–291. doi: 10.1016/0141-8130(88)90006-2 CrossRefGoogle Scholar
  13. Cazzola F, Corsa V, O’Regan M (2003) Culture medium and process for the preparation of high molecular weight hyaluronic acid. EP071668B1Google Scholar
  14. Chen WY, Marcellin E, Hung J, Nielsen LK (2009) Hyaluronan molecular weight is controlled by UDP-N-acetylglucosamine concentration in Streptococcus zooepidemicus. J Biol Chem 284:18007–18014. doi: 10.1074/jbc.M109.011999 PubMedCentralPubMedCrossRefGoogle Scholar
  15. Chen WY, Marcellin E, Steen JA, Nielsen LK (2014) The role of hyaluronic acid precursor concentrations in molecular weight control in Streptococcus zooepidemicus. Mol Biotechnol 56:147–156. doi: 10.1007/s12033-013-9690-4 PubMedCrossRefGoogle Scholar
  16. Chien L-J, Lee C-K (2007) Hyaluronic acid production by recombinant Lactococcus lactis. Appl Microbiol Biotechnol 77:339–346. doi: 10.1007/s00253-007-1153-z PubMedCrossRefGoogle Scholar
  17. Chong BF, Nielsen LK (2003a) Aerobic cultivation of Streptococcus zooepidemicus and the role of NADH oxidase. Biochem Eng J 16:153–162. doi: 10.1016/S1369-703x(03)00031-7 CrossRefGoogle Scholar
  18. Chong BF, Nielsen LK (2003b) Amplifying the cellular reduction potential of Streptococcus zooepidemicus. J Biotechnol 100:33–41. doi: 10.1016/S0168-1656(02)00239-0 PubMedCrossRefGoogle Scholar
  19. Chong BF, Blank LM, McLaughlin R, Nielsen LK (2005) Microbial hyaluronic acid production. Appl Microbiol Biotechnol 66:341–351. doi: 10.1007/s00253-004-1774-4 PubMedCrossRefGoogle Scholar
  20. Choudhary M, Zhang X, Stojkovic P, Hyslop L, Anyfantis G, Herbert M, Murdoch AP, Stojkovic M, Lako M (2007) Putative role of hyaluronan and its related genes, HAS2 and RHAMM, in human early preimplantation embryogenesis and embryonic stem cell characterization. Stem Cells 25:3045–3057. doi: 10.1634/stemcells.2007-0296 PubMedCrossRefGoogle Scholar
  21. Chung JY, Zhang Y, Adler B (1998) The capsule biosynthetic locus of Pasteurella multocida A:1. FEMS Microbiol Lett 166:289–296. doi: 10.1111/j.1574-6968.1998.tb13903.x PubMedCrossRefGoogle Scholar
  22. Collins MN, Birkinshaw C (2013) Hyaluronic acid solutions—a processing method for efficient chemical modification. J Appl Polym Sci. doi: 10.1002/app.39145 Google Scholar
  23. DeAngelis PL (2008) Monodisperse hyaluronan polymers: synthesis and potential applications. Curr Pharm Biotechnol 9:246–248. doi: 10.2174/138920108785161550 PubMedCrossRefGoogle Scholar
  24. DeAngelis PL, Papaconstantinou J, Weigel PH (1993) Molecular cloning, identification, and sequence of the hyaluronan synthase gene from group A Streptococcus pyogenes. J Biol Chem 268:19181–19184PubMedGoogle Scholar
  25. DeAngelis PL, Jing W, Graves MV, Burbank DE, Van Etten JL (1997) Hyaluronan synthase of Chlorella virus PBCV-1. Science 278:1800–1803. doi: 10.1126/science.278.5344.1800 PubMedCrossRefGoogle Scholar
  26. DeAngelis PL, Jing W, Drake RR, Achyuthan AM (1998) Identification and molecular cloning of a unique hyaluronan synthase from Pasteurella multocida. J Biol Chem 273:8454–8458. doi: 10.1074/jbc.273.14.8454 PubMedCrossRefGoogle Scholar
  27. DeAngelis PL, Oatman LC, Gay DF (2003) Rapid chemoenzymatic synthesis of monodisperse hyaluronan oligosaccharides with immobilized enzyme reactors. J Biol Chem 278:35199–35203. doi: 10.1074/jbc.M306431200 PubMedCrossRefGoogle Scholar
  28. Dougherty BA, van de Rijn I (1994) Molecular characterization of hasA from an operon required for hyaluronic acid synthesis in group A streptococci. J Biol Chem 269:169–175PubMedGoogle Scholar
  29. Duan XJ, Yang L, Zhang X, Tan WS (2008) Effect of oxygen and shear stress on molecular weight of hyaluronic acid. J Microbiol Biotechnol 18:718–724PubMedGoogle Scholar
  30. Duan XJ, Niu HX, Tan WS, Zhang X (2009) Mechanism analysis of effect of oxygen on molecular weight of hyaluronic acid produced by Streptococcus zooepidemicus. J Microbiol Biotechnol 19:299–306PubMedGoogle Scholar
  31. Fassel TA, Mozdziak PE, Sanger JR, Edmiston CE (1998) Superior preservation of the staphylococcal glycocalyx with aldehyde-ruthenium red and select lysine salts using extended fixation times. Microsc Res Tech 41(4):291–297. doi: 10.1002/(SICI)1097-0029(19980515)41:4<291::AID-JEMT2>3.0.CO;2-U.
  32. Fraser JR, Laurent TC, Laurent UB (1997) Hyaluronan: its nature, distribution, functions and turnover. J Intern Med 242:27–33PubMedCrossRefGoogle Scholar
  33. Gibbs DA, Merrill EW, Smith KA, Balazs EA (1968) Rheology of hyaluronic acid. Biopolymers 6:777–791. doi: 10.1002/bip.1968.360060603 PubMedCrossRefGoogle Scholar
  34. Goa KL, Benfield P (1994) Hyaluronic acid—a review of its pharmacology and use as a surgical aid in ophthalmology, and its therapeutic potential in joint disease and wound-healing. Drugs 47:536–566PubMedCrossRefGoogle Scholar
  35. Harper M, Boyce JD, Adler B (2006) Pasteurella multocida pathogenesis: 125 years after Pasteur. FEMS Microbiol Lett 265:1–10. doi: 10.1111/j.1574-6968.2006.00442.x PubMedCrossRefGoogle Scholar
  36. Huang WC, Chen S-J, Chen T-L (2006) The role of dissolved oxygen and function of agitation in hyaluronic acid fermentation. Biochem Eng J 32:239–243. doi: 10.1016/j.bej.2006.10.011 CrossRefGoogle Scholar
  37. Hubbard C, McNamara JT, Azumaya C, Patel MS, Zimmer J (2012) The hyaluronan synthase catalyzes the synthesis and membrane translocation of hyaluronan. J Mol Biol 418:21–31. doi: 10.1016/j.jmb.2012.01.053 PubMedCrossRefGoogle Scholar
  38. Huszar G, Ozkavukcu S, Jakab A, Celik-Ozenci C, Sati GL, Cayli S (2006) Hyaluronic acid binding ability of human sperm reflects cellular maturity and fertilizing potential: selection of sperm for intracytoplasmic sperm injection. Curr Opin Obstet Gynecol 18:260–267. doi: 10.1097/01.gco.0000193018.98061.2f PubMedCrossRefGoogle Scholar
  39. Itano N, Kimata K (1996) Molecular cloning of human hyaluronan synthase. Biochem Biophys Res Commun 222:816–820. doi: 10.1006/bbrc.1996.0827 PubMedCrossRefGoogle Scholar
  40. Itano N, Kimata K (2002) Mammalian hyaluronan synthases. IUBMB Life 54:195–199. doi: 10.1080/15216540214929 PubMedCrossRefGoogle Scholar
  41. Itano N, Sawai T, Yoshida M, Lenas P, Yamada Y, Imagawa M, Shinomura T, Hamaguchi M, Yoshida Y, Ohnuki Y, Miyauchi S, Spicer AP, McDonald JA, Kimata K (1999) Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties. J Biol Chem 274:25085–25092. doi: 10.1074/jbc.274.35.25085 PubMedCrossRefGoogle Scholar
  42. Jia Y, Zhu J, Chen X, Tang D, Su D, Yao W, Gao X (2013) Metabolic engineering of Bacillus subtilis for the efficient biosynthesis of uniform hyaluronic acid with controlled molecular weights. Bioresour Technol 132:427–431. doi: 10.1016/j.biortech.2012.12.150 PubMedCrossRefGoogle Scholar
  43. Jing W, DeAngelis PL (2000) Dissection of the two transferase activities of the Pasteurella multocida hyaluronan synthase: two active sites exist in one polypeptide. Glycobiology 10:883–889PubMedCrossRefGoogle Scholar
  44. Jing WF, DeAngelis PL (2004) Synchronized chemoenzymatic synthesis of monodisperse hyaluronan polymers. J Biol Chem 40:42345–42349. doi: 10.1074/jbc.M402744200 CrossRefGoogle Scholar
  45. Juhlin L (1997) Hyaluronan in skin. J Intern Med 242:61–66PubMedCrossRefGoogle Scholar
  46. Ke C, Wang D, Sun Y, Qiao D, Ye H, Zeng X (2013) Immunostimulatory and antiangiogenic activities of low molecular weight hyaluronic acid. Food Chem Toxicol 58:401–407. doi: 10.1016/j.fct.2013.05.032 S0278-6915(13)00338-4 PubMedCrossRefGoogle Scholar
  47. Kim J-H, Yoo S-J, Oh D-K, Kweon Y-G, Park D-W, Lee C-H, Gil G-H (1996) Selection of a Streptococcus equi mutant and optimization of culture conditions for the production of high molecular weight hyaluronic acid. Enzym Microb Techmol 19:440–445. doi: 10.1016/S0141-0229(96)00019-1 CrossRefGoogle Scholar
  48. Kim SJ, Park SY, Kim CW (2006) A novel approach to the production of hyaluronic acid by Streptococcus zooepidemicus. J Microbiol Biotechnol 16:1849–1855Google Scholar
  49. Kumari K, Weigel PH (1997) Molecular cloning, expression, and characterization of the authentic hyaluronan synthase from Group C Streptococcus equisimilis. J Biol Chem 272:32539–32546. doi: 10.1074/jbc.272.51.32539 PubMedCrossRefGoogle Scholar
  50. Kumari K, Baggenstoss BA, Parker AL, Weigel PH (2006) Mutation of two intramembrane polar residues conserved within the hyaluronan synthase family alters hyaluronan product size. J Biol Chem 281:11755–11760. doi: 10.1074/jbc.M600727200 PubMedCrossRefGoogle Scholar
  51. Levin JC, Wessels MR (1998) Identification of csrR/csrS, a genetic locus that regulates hyaluronic acid capsule synthesis in group A Streptococcus. Mol Microbiol 30:209–219PubMedCrossRefGoogle Scholar
  52. Lokeshwar VB, Cerwinka WH, Isoyama T, Lokeshwar BL (2005) HYAL1 hyaluronidase in prostate cancer: a tumor promoter and suppressor. Cancer Res 65:7782–7789. doi: 10.1158/0008-5472.CAN-05-1022 PubMedCrossRefGoogle Scholar
  53. Luo Y, Kirker KR, Prestwich GD (2000) Cross-linked hyaluronic acid hydrogel films: new biomaterials for drug delivery. J Control Release 69:169–184PubMedCrossRefGoogle Scholar
  54. Mao Z, Chen RR (2007) Recombinant synthesis of hyaluronan by Agrobacterium sp. Biotechnol Prog 23:1038–1042. doi: 10.1021/bp070113n PubMedGoogle Scholar
  55. Marcellin E, Nielsen LK, Abeydeera P, Krömer JO (2009) Quantitative analysis of intracellular sugar phosphates and sugar nucleotides in encapsulated streptococci using HPAEC-PAD. Biotechnol J 4:58–63. doi: 10.1002/biot.200800197 PubMedCrossRefGoogle Scholar
  56. Marcellin E, Chen WY, Nielsen LK (2010) Understanding plasmid effect on hyaluronic acid molecular weight produced by Streptococcus equi subsp. zooepidemicus. Metab Eng 12:62–69. doi: 10.1016/j.ymben.2009.09.001 PubMedCrossRefGoogle Scholar
  57. McIver KS, Scott JR (1997) Role of Mga in growth phase regulation of virulence genes of the group A streptococcus. J Bacteriol 179:5178–5187PubMedCentralPubMedGoogle Scholar
  58. Mendichi R, Soltes L, Giacometti Schieroni A (2003) Evaluation of radius of gyration and intrinsic viscosity molar mass dependence and stiffness of hyaluronan. Biomacromolecules 4:1805–1810. doi: 10.1021/bm0342178 PubMedCrossRefGoogle Scholar
  59. Meyer MF, Kreil G (1996) Cells expressing the DG42 gene from early Xenopus embryos synthesize hyaluronan. Proc Natl Acad Sci U S A 93:4543–4547PubMedCentralPubMedCrossRefGoogle Scholar
  60. Meyer K, Palmer JW (1934) The polysaccharide of the vitreous humor. J Biol Chem 107:629–634Google Scholar
  61. Moon MH (2010) Flow field-flow fractionation and multiangle light scattering for ultrahigh molecular weight sodium hyaluronate characterization. J Sep Sci 33:3519–3529. doi: 10.1002/jssc.201000414 PubMedCrossRefGoogle Scholar
  62. Moon MH, da Shin Y, Lee N, Hwang E, Cho IH (2008) Flow field-flow fractionation/multiangle light scattering of sodium hyaluronate from various degradation processes. J Chromatogr B Anal Technol Biomed Life Sci 864:15–21. doi: 10.1016/j.jchromb.2008.01.023 CrossRefGoogle Scholar
  63. Nagahashi S, Sudoh M, Ono N, Sawada R, Yamaguchi E, Uchida Y, Mio T, Takagi M, Arisawa M, Yamada-Okabe H (1995) Characterization of chitin synthase 2 of Saccharomyces cerevisiae. Implication of two highly conserved domains as possible catalytic sites. J Biol Chem 270:13961–13967PubMedCrossRefGoogle Scholar
  64. Noble PW (2002) Hyaluronan and its catabolic products in tissue injury and repair. Matrix Biol 21:25–29. doi: 10.1016/S0945-053X(01)00184-6 PubMedCrossRefGoogle Scholar
  65. Ogston AG, Stanier JE (1950) On the state of hyaluronic acid in synovial fluid. Biochem J 46:364–376PubMedCentralPubMedGoogle Scholar
  66. Park MG, Jang JD, Kang WK (1996) Streptococcus zooepidemicus medium and process for preparing hyaluronic acid. USPT 5:496,726Google Scholar
  67. Rooney P, Kumar S, Ponting J, Wang M (1995) The role of hyaluronan in tumour neovascularization. Int J Cancer 60:632–636PubMedCrossRefGoogle Scholar
  68. Santillan DA, Andracki ME, Hunter SK (2008) Protective immunization in mice against group B streptococci using encapsulated C5a peptidase. Am J Obstet Gynecol 198(114):e111–e116. doi: 10.1016/j.ajog.2007.06.003 Google Scholar
  69. Schanté CE, Zuber G, Herlin C, Vandamme TF (2011) Chemical modifications of hyaluronic acid for the synthesis of derivatives for a broad range of biomedical applications. Carbohydr Polym 85:469–489. doi: 10.1016/j.carbpol.2011.03.019 CrossRefGoogle Scholar
  70. Sheng JZ, Ling PX, Zhu XQ, Guo XP, Zhang TM, He YL, Wang FS (2009) Use of induction promoters to regulate hyaluronan synthase and UDP-glucose-6-dehydrogenase of Streptococcus zooepidemicus expression in Lactococcus lactis: a case study of the regulation mechanism of hyaluronic acid polymer. J Appl Microbiol 107:136–144. doi: 10.1111/j.1365-2672.2009.04185.x PubMedCrossRefGoogle Scholar
  71. Speranza A, Pellizzaro C, Coradini D (2005) Hyaluronic acid butyric esters in cancer therapy. Anti-Cancer Drugs 16:373–379PubMedCrossRefGoogle Scholar
  72. Steen JA, Steen JA, Harrison P, Seemann T, Wilkie I, Harper M, Adler B, Boyce JD (2010) Fis is essential for capsule production in Pasteurella multocida and regulates expression of other important virulence factors. PLoS Pathog 6:e1000750. doi: 10.1371/journal.ppat.1000750 PubMedCentralPubMedCrossRefGoogle Scholar
  73. Stern R, Asari AA, Sugahara KN (2006) Hyaluronan fragments: an information-rich system. Eur J Cell Biol 85:699–715. doi: 10.1016/j.ejcb.2006.05.009 PubMedCrossRefGoogle Scholar
  74. Stollerman GH, Dale JB (2008) The importance of the group A Streptococcus capsule in the pathogenesis of human infections: a historical perspective. Clin Infect Dis 46:1038–1045. doi: 10.1086/529194 PubMedCrossRefGoogle Scholar
  75. Sugahara KN, Murai T, Nishinakamura H, Kawashima H, Saya H, Miyasaka M (2003) Hyaluronan oligosaccharides induce CD44 cleavage and promote cell migration in CD44-expressing tumor cells. J Biol Chem 278:32259–32265. doi: 10.1074/jbc.M300347200 PubMedCrossRefGoogle Scholar
  76. Thomas NK, Brown TJ (2010) ABC transporters do not contribute to extracellular translocation of hyaluronan in human breast cancer in vitro. Exp Cell Res 316:1241–1253. doi: 10.1016/j.yexcr.2010.01.004 PubMedCrossRefGoogle Scholar
  77. Tian X, Azpurua J, Hine C, Vaidya A, Myakishev-Rempel M, Ablaeva J, Mao ZY, Nevo E, Gorbunova V, Seluanov A (2013) High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature 499(7458):346–349. doi: 10.1038/nature12234
  78. Tlapak-Simmons VL, Kempner ES, Baggenstoss BA, Weigel PH (1998) The active streptococcal hyaluronan synthases (HASs) contain a single HAS monomer and multiple cardiolipin molecules. J Biol Chem 273:26100–26109. doi: 10.1074/jbc.273.40.26100 PubMedCrossRefGoogle Scholar
  79. Tlapak-Simmons VL, Baggenstoss BA, Clyne T, Weigel PH (1999a) Purification and lipid dependence of the recombinant hyaluronan synthases from Streptococcus pyogenes and Streptococcus equisimilis. J Biol Chem 274:4239–4245. doi: 10.1074/jbc.274.7.4239 PubMedCrossRefGoogle Scholar
  80. Tlapak-Simmons VL, Baggenstoss BA, Kumari K, Heldermon C, Weigel PH (1999b) Kinetic characterization of the recombinant hyaluronan synthases from Streptococcus pyogenes and Streptococcus equisimilis. J Biol Chem 274:4246–4253. doi: 10.1074/jbc.274.7.4246 PubMedCrossRefGoogle Scholar
  81. Tlapak-Simmons VL, Baron CA, Weigel PH (2004) Characterization of the purified hyaluronan synthase from Streptococcus equisimilis. Biochemistry 43:9234–9242. doi: 10.1021/bi049468v PubMedCentralPubMedCrossRefGoogle Scholar
  82. Tlusta M, Krahulec J, Pepeliaev S, Franke L, Cerny Z, Jilkova J (2013) Production of hyaluronic acid by mutant strains of group C Streptococcus. Mol Biotechnol 54:747–755. doi: 10.1007/s12033-012-9622-8 PubMedCrossRefGoogle Scholar
  83. Vabres P (2010) Hyaluronan, embryogenesis and morphogenesis. Ann Dermatol Venereol 137(Suppl 1):S9–S14. doi: 10.1016/S0151-9638(10)70003-X PubMedCrossRefGoogle Scholar
  84. Videbaek T Novozymes’ Capital Markets Day. In, (2011). http://www.novozymes.com/en/investor/eventspresentations/Documents/10_NZCMD_TVI_Hyaluronic%20Acid_FINAL.pdf/. Accessed 04 June 2014
  85. Watanabe K, Yamaguchi Y (1996) Molecular identification of a putative human hyaluronan synthase. J Biol Chem 271:22945–22948. doi: 10.1074/jbc.271.38.22945
  86. Weigel PH (2004) The hyaluronan synthases. In: Garg HG, Hales CA (eds) Chemistry and biology of hyaluronan. Elsevier Ltd, Oxford, pp 553–568CrossRefGoogle Scholar
  87. Weigel PH, DeAngelis PL (2007) Hyaluronan synthases: a decade-plus of novel glycosyltransferases. J Biol Chem 282:36777–36781. doi: 10.1074/jbc.R700036200 PubMedCrossRefGoogle Scholar
  88. Weigel PH, Hascall VC, Tammi M (1997) Hyaluronan synthases. J Biol Chem 272:13997–14000PubMedCrossRefGoogle Scholar
  89. Weissmann B, Meyer K (1954) The structure of hyaluronic acid and of hyaluronic acid from umbilical cord. J Am Chem Soc 76:1753–1757. doi: 10.1021/Ja01636a010 CrossRefGoogle Scholar
  90. Widner B, Behr R, Von Dollen S, Tang M, Heu T, Sloma A, Sternberg D, DeAngelis PL, Weigel PH, Brown S (2005) Hyaluronic acid production in Bacillus subtilis. Appl Environ Microbiol 71:3747–3752. doi: 10.1128/AEM.71.7.3747-3752.2005 PubMedCentralPubMedCrossRefGoogle Scholar
  91. Wu TF, Huang WC, Chen YC, Tsay YG, Chang CS (2009) Proteomic investigation of the impact of oxygen on the protein profiles of hyaluronic acid-producing Streptococcus zooepidemicus. Proteomics 9:4507–4518. doi: 10.1002/pmic.200800868 PubMedCrossRefGoogle Scholar
  92. Yu H, Stephanopoulos G (2008) Metabolic engineering of Escherichia coli for biosynthesis of hyaluronic acid. Metab Eng 10:24–32. doi: 10.1016/j.ymben.2007.09.001 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Esteban Marcellin
    • 1
    Email author
  • Jennifer A. Steen
    • 1
  • Lars K. Nielsen
    • 1
  1. 1.Australian Institute for Bioengineering and Nanotechnology (AIBN)The University of QueenslandBrisbaneAustralia

Personalised recommendations