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Hyaluronic acid production in Bacillus subtilis.

Applied and Environmental Microbiology

genetics, Bacillus subtilis, enzymology, Bioreactors, Fermentation, Glucuronosyltransferase, metabolism, Hyaluronic Acid, biosynthesis, Industrial Microbiology, methods, Laboratories, Recombinant Proteins, Streptococcus

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      The hasA gene from Streptococcus equisimilis, which encodes the enzyme hyaluronan synthase, has been expressed in Bacillus subtilis, resulting in the production of hyaluronic acid (HA) in the 1-MDa range. Artificial operons were assembled and tested, all of which contain the hasA gene along with one or more genes encoding enzymes involved in the synthesis of the UDP-precursor sugars that are required for HA synthesis. It was determined that the production of UDP-glucuronic acid is limiting in B. subtilis and that overexpressing the hasA gene along with the endogenous tuaD gene is sufficient for high-level production of HA. In addition, the B. subtilis-derived material was shown to be secreted and of high quality, comparable to commercially available sources of HA.

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