An enzyme library approach to biocatalysis: development of nitrilases for enantioselective production of carboxylic acid derivatives.
An enzyme library approach to biocatalysis: development of nitrilases for enantioselective production of carboxylic acid derivatives.
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DOI：
10.1021/ja0251120
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发表时间：
2002-10
影响因子：
15
通讯作者：
G. Desantis;Zuolin Zhu;W. A. Greenberg;Kelvin Wong;J. Chaplin;S. Hanson;B. Farwell;L. W. Nicholson;C. Rand;D. Weiner;D. Robertson;M. Burk
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文献类型：
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作者：
G. Desantis;Zuolin Zhu;W. A. Greenberg;Kelvin Wong;J. Chaplin;S. Hanson;B. Farwell;L. W. Nicholson;C. Rand;D. Weiner;D. Robertson;M. Burk
报道了在自然界中发现的大量不同的腈水解酶。证明了该腈水解酶库用于鉴定催化有效生产有价值的羟基羧酸衍生物的酶的效用。强调了三种新发现且不同的腈水解酶前所未有的对映选择性和底物范围。例如，以高速率、产率和对映体过量（95- 99%ee）生产了广泛的（R）-扁桃酸衍生物和类似物。我们还发现了腈水解酶，其提供直接获得（S）-苯基乳酸和其它芳基乳酸衍生物的途径，同样具有高产率和对映选择性。最后，已经发现不同的腈水解酶催化3-羟基戊二腈的对映体水解，得到具有高对映体过量（> 95%ee）的4-氰基-3-羟基丁酸的任一对映体。据报道，第一种酶实现了这种转化，提供了（R）-4-氰基-3-羟基丁酸，它是畅销药物立普妥的前体。
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.