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Applied and Environmental Microbiology, July 2005, p. 3747-3752, Vol. 71, No. 7
0099-2240/05/$08.00+0     doi:10.1128/AEM.71.7.3747-3752.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Hyaluronic Acid Production in Bacillus subtilis

Bill Widner,1* Régine Behr,1 Steve Von Dollen,1 Maria Tang,1 Tia Heu,1 Alan Sloma,1 Dave Sternberg,1 Paul L. DeAngelis,2 Paul H. Weigel,2 and Steve Brown1

Novozymes, Inc., 1445 Drew Avenue, Davis, California 95616,1 Department of Biochemistry and Molecular Biology and the Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd., Oklahoma City, Oklahoma 731042

Received 19 August 2004/ Accepted 4 January 2005

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.

* Corresponding author. Mailing address: Novozymes, Inc., 1445 Drew Avenue, Davis, CA 95616. Phone: (530) 757-8129. Fax: (530) 758-0317. E-mail: wwi{at}novozymes.com.

Applied and Environmental Microbiology, July 2005, p. 3747-3752, Vol. 71, No. 7
0099-2240/05/$08.00+0     doi:10.1128/AEM.71.7.3747-3752.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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