An enzyme library approach to biocatalysis: Development of nitrilases for enantioselective production of carboxylic acid derivatives

被引：201

作者：

DeSantis, G ^{[1
]}

Zhu, ZL ^{[1
]}

Greenberg, WA ^{[1
]}

Wong, KV ^{[1
]}

Chaplin, J ^{[1
]}

Hanson, SR ^{[1
]}

Farwell, B ^{[1
]}

Nicholson, LW ^{[1
]}

Rand, CL ^{[1
]}

Weiner, DP ^{[1
]}

Robertson, DE ^{[1
]}

Burk, MJ ^{[1
]}

机构：

[1] Diversa Corp, San Diego, CA 92121 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2002年 / 124卷 / 31期

关键词：

D O I：

10.1021/ja0259842

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The discovery, from Nature, of a large and diverse set of nitrilases is reported. The utility of this nitrilase library for identifying enzymes that catalyze efficient production of valuable hydroxy carboxylic acid derivatives is demonstrated. Unprecedented enantioselectivity and substrate scope are highlighted for three newly discovered and distinct nitrilases. For example, a wide array of (R)-mandelic acid derivatives and analogues were produced with high rates, yields, and enantiomeric excesses (95-99% ee). We also have found nitrilases that provide direct access to (S)-phenyllactic acid and other aryllactic acid derivatives, again with high yields and enantioselectivities. Finally, different nitrilases have been discovered that catalyze enantiotopic hydrolysis of 3-hydroxyglutaronitrile to afford either enantiomer of 4-cyano-3-hydroxybutyric acid with high enantiomeric excesses (>95% ee). The first enzymes are reported that effect this transformation to furnish the (R)-4-cyano-3-hydroxybutyric acid which is a precursor to the blockbuster drug Lipitor. Copyright © 2002 American Chemical Society.

引用

页码：9024 / 9025

页数：2

共 26 条

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