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生物催化酮还原——生产手性醇的强大工具——第二部分:全细胞还原

Biocatalytic ketone reduction--a powerful tool for the production of chiral alcohols-part II: whole-cell reductions.

作者信息

Goldberg Katja, Schroer Kirsten, Lütz Stephan, Liese Andreas

机构信息

Institute of Technical Biocatalysis, Hamburg University of Technology, 21073 Hamburg, Germany.

出版信息

Appl Microbiol Biotechnol. 2007 Aug;76(2):249-55. doi: 10.1007/s00253-007-1005-x. Epub 2007 May 8.

DOI:10.1007/s00253-007-1005-x
PMID:17486338
Abstract

Enzymes are able to perform reactions under mild conditions, e.g., pH and temperature, with remarkable chemo-, regio-, and stereoselectivity. Due to this feature the number of biocatalysts used in organic synthesis has rapidly increased during the last decades, especially for the production of chiral compounds. The present review highlights biotechnological processes for the production of chiral alcohols by reducing prochiral ketones with whole cells. Microbial transformations feature different characteristics in comparison to isolated enzymes. Enzymes that are used in whole-cell biotransformations are often more stable due to the presence of their natural environment inside the cell. Because reductase-catalyzed reactions are dependent on cofactors, one major task in process development is to provide an effective method for regeneration of the consumed cofactors. Many whole-cell biocatalysts offer their internal cofactor regeneration that can be used by adding cosubstrates, glucose or, in the case of cyanobacteria, simply light. In this paper, various processes carried out on laboratory and industrial scales are presented. Thereby, attention is turned to process parameters, e.g., conversion, yield, enantiomeric excess, and process strategies, e.g., the application of biphasic systems. The biocatalytic production of chiral alcohols utilizing isolated enzymes is presented in part I of this review.

摘要

酶能够在温和的条件下(例如pH值和温度)进行反应,具有显著的化学、区域和立体选择性。由于这一特性,在过去几十年中,有机合成中使用的生物催化剂数量迅速增加,尤其是用于手性化合物的生产。本综述重点介绍了通过用全细胞还原前手性酮来生产手性醇的生物技术过程。与分离的酶相比,微生物转化具有不同的特点。由于细胞内自然环境的存在,全细胞生物转化中使用的酶通常更稳定。因为还原酶催化的反应依赖于辅因子,所以过程开发中的一项主要任务是提供一种有效的方法来再生消耗的辅因子。许多全细胞生物催化剂提供其内部的辅因子再生,可通过添加共底物、葡萄糖来实现,或者对于蓝细菌而言,仅通过光照即可。本文介绍了在实验室和工业规模上进行的各种过程。因此,注意力转向了过程参数,例如转化率、产率、对映体过量,以及过程策略,例如双相系统的应用。本综述的第一部分介绍了利用分离的酶进行手性醇的生物催化生产。

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