Hyaluronan Molecular Weight Is Controlled by UDP-N-acetylglucosamine Concentration in Streptococcus zooepidemicus

Chen, Wendy Yiting, Marcellin, Esteban, Hung, Jacky and Nielsen, Lars Keld (2009) Hyaluronan Molecular Weight Is Controlled by UDP-N-acetylglucosamine Concentration in Streptococcus zooepidemicus. Journal of Biological Chemistry, 284 27: 18007-18014. doi:10.1074/jbc.M109.011999

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Author Chen, Wendy Yiting
Marcellin, Esteban
Hung, Jacky
Nielsen, Lars Keld
Title Hyaluronan Molecular Weight Is Controlled by UDP-N-acetylglucosamine Concentration in Streptococcus zooepidemicus
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2009-07-03
Year available 2009
Sub-type Article (original research)
DOI 10.1074/jbc.M109.011999
Open Access Status File (Publisher version)
Volume 284
Issue 27
Start page 18007
End page 18014
Total pages 8
Editor Herbert Tabor
Place of publication United States
Publisher American society for Biochemistry and Molecular Biology
Language eng
Subject C1
Abstract The molecular weight of hyaluronan is important for its rheological and biological function. The molecular mechanisms underlying chain termination and hence molecular weight control remain poorly understood, not only for hyaluronan synthases but also for other beta-polysaccharide synthases, e. g. cellulose, chitin, and 1,3-betaglucan synthases. In this work, we manipulated metabolite concentrations in the hyaluronan pathway by overexpressing the five genes of the hyaluronan synthesis operon in Streptococcus equi subsp. zooepidemicus. Overexpression of genes involved in UDP-glucuronic acid biosynthesis decreased molecular weight, whereas overexpression of genes involved in UDP-N-acetylglucosamine biosynthesis increased molecular weight. The highest molecular mass observed was at 3.4 +/- 0.1 MDa twice that observed in the wild-type strain, 1.8 +/- 0.1 MDa. The data indicate that (a) high molecular weight is achieved when an appropriate balance of UDP-N-acetylglucosamine and UDP-glucuronic acid is achieved, (b) UDP-N-acetylglucosamine exerts the dominant effect on molecular weight, and (c) the wild-type strain has suboptimal levels of UDP-Nacetylglucosamine. Consistent herewith molecular weight correlated strongly (rho = 0.84, p = 3 x 10(-5)) with the concentration of UDP-N-acetylglucosamine. Data presented in this paper represent the first model for hyaluronan molecular weight control based on the concentration of activated sugar precursors. These results can be used to engineer strains producing high molecular weight hyaluronan and may provide insight into similar polymerization mechanisms in other polysaccharides. (C)2009 by The American Society for Biochemistry and Molecular Biology, Inc.
Keyword Group-a Streptococci
Acid production
Sodium Hyaluronate
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Australian Institute for Bioengineering and Nanotechnology Publications
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Citation counts: TR Web of Science Citation Count  Cited 46 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 03 Sep 2009, 17:50:35 EST by Mr Andrew Martlew on behalf of Aust Institute for Bioengineering & Nanotechnology