? Enantiopure epoxides and vicinal diols are valuable, but difficult to synthesize building blocks for fine chemical and numerous pharmaceuticals. Epoxide hydrolases, which catalyze the hydrolysis of racemic epoxides to generate both the corresponding diols and the un-reacted epoxides, are promising biocatalysts for use in the preparation of these compounds. Fewer than fifteen microbial epoxide hydrolases have been characterized and reported to date. Several epoxide hydrolases previously have been explored for the preparation of enantiomerically pure epoxides and vicinal diols, but little progress has been made in the development of these enzymes as viable synthetic tools. This application proposes the discovery of a large and diverse set of epoxide hydrolases and subsequent development of best enzymes for industrial application. In this proposal, a number of powerful high-throughput screening technologies will be developed for the discovery of microbial epoxide hydrolases from Diversa's environmental DNA libraries. The sequences of the discovered enzymes will be determined, and the enzymes will be assayed for their activities on a variety of commercially important epoxides. The overall goal of this project is to create an epoxide hydrolase platform, which consists of a large array of novel epoxide hydrolases with diverse substrate scope and enantioselectivity. The availability of a library of natural epoxide hydrolases, together with those resulted from directed evolution technologies will open up numerous opportunities in their synthetic utilization in fine chemical and pharmaceutical industry. ? ?
| Zhao, Lishan; Han, Bin; Huang, Zilin et al. (2004) Epoxide hydrolase-catalyzed enantioselective synthesis of chiral 1,2-diols via desymmetrization of meso-epoxides. lzhao@diversa.com. J Am Chem Soc 126:11156-7 |
