Hyaluronic acid production in Bacillus subtilis.
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.
Widner
Bill
B
Novozymes, Inc., 1445 Drew Avenue, Davis, CA 95616, USA. wwi@novozymes.com
Behr
Régine
R
Von Dollen
Steve
S
Tang
Maria
M
Heu
Tia
T
Sloma
Alan
A
Sternberg
Dave
D
Deangelis
Paul L
PL
Weigel
Paul H
PH
Brown
Steve
S
D001412:Bacillus subtilis / Q000201:enzymology* / Q000235:genetics*; D019149:Bioreactors; D005285:Fermentation; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D007218:Industrial Microbiology / Q000379:methods; D007753:Laboratories; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013291:Streptococcus / Q000201:enzymology / Q000235:genetics
D011994:Recombinant Proteins; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases