This research will develop enzymatic catalysts for the synthesis of bioactive molecules. It will focus on the following programs: 1. Develop catalytic asymmetric aldol condensations based on aldolases, particularly E. coli fructose- 1,6-diphosphate aldolase, tagatose- 1,6-diphosphate aldolase, sialic acid aldolase and synthetase, 2-deoxyribose-5-phosphate aldolase, and KDO aldolase, for the synthesis of monosaccharides and analogs. 2. Develop asymmetric glycosylations based on glycosyltransferases for the synthesis of oligosaccharides and nucleosides. 3. Use genetic engineering to improve the production and performance of synthetically useful enzymes, particularly subtilisin, glycosyltransferases, and aldolases. 4. Develop new methods for using enzyme products for synthesis of natural products and designed molecules: glycosidase and glycosyltransferase inhibitors, unique sugars from G(-) bacteria, sialyl Le-x and other oligosaccharides, carbocyclic derivatives of sugars, antibiotics and glycopeptides. 5. Provide other enzymatic and non-enzymatic reactions, NMR and modeling techniques to support these efforts in synthesis and molecular design. Significant contributions in the areas of biomedicine and, synthetic organic chemistry are expected. These developments may facilitate the discovery and development of new therapeutic agents.
| Lewis, Jared C; Bastian, Sabine; Bennett, Clay S et al. (2009) Chemoenzymatic elaboration of monosaccharides using engineered cytochrome P450BM3 demethylases. Proc Natl Acad Sci U S A 106:16550-5 |
| Hanson, Sarah R; Culyba, Elizabeth K; Hsu, Tsui-Ling et al. (2009) The core trisaccharide of an N-linked glycoprotein intrinsically accelerates folding and enhances stability. Proc Natl Acad Sci U S A 106:3131-6 |
