POLY 633 |
| Gram-negative Pasteurella multocida bacteria produce extracellular coatings (capsules) composed of glycosaminoglycan (GAG) polysaccharides including hyaluronan (HA), chondroitin, and heparosan. These linear polysaccharides are also components of many vertebrate tissues, thus bacterial capsules serve as molecular camouflage to render host defenses less effective. Several current medical therapies and surgeries employ naturally occurring GAGs resulting in a growing multi-billion$/year market. Now, new systems for producing recombinant GAGs have been developed by harnessing the bacterial systems via fermentation in vivo or via chemoenzymatic synthesis in vitro. GAG synthase genes have been transferred into Gram-positive Bacillus subtilis, a safe ‘workhorse' microbe thus forming recombinant HA, chondroitin, or heparosan fermentation systems. Chemoenzymatic methods to construct monodisperse 0.01-2,000 kDa polysaccharides with synchronized reactions were developed. We have also created oligosaccharide (5- to 22-mers) synthesis systems employing mutant enzymes in a step-wise sugar addition strategy. Overall, safer, more defined GAG polymers will facilitate various medical applications. |
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Biocatalysis in Polymer Science
1:30 PM-4:45 PM, Wednesday, 13 September 2006 San Francisco Marriott -- Salon 12/13, Oral
Division of Polymer Chemistry |