文献类型：期刊文献

英文题名：Whole-Cell-Catalyzed Multiple Regio- and Stereoselective Functionalizations in Cascade Reactions Enabled by Directed Evolution

作者：Li, Aitao[1,2];Ilie, Adriana[1,2];Sun, Zhoutong[1,2];Lonsdale, Richard[1,2];Xu, Jian-He[3];Reetz, Manfred T.[1,2]

机构：[1]Max Planck Inst Kohlenforsch, Kaiser Wilhelm Pl 1, D-45470 Mulheim, Germany;[2]Univ Marburg, Fachbereich Chem, Hans Meerwein Str, D-35032 Marburg, Germany;[3]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2016

卷号：55

期号：39

起止页码：12026

外文期刊名：ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

收录：;EI(收录号：20164302954753);WOS:【SCI-EXPANDED(收录号:WOS:000384713100060)】；

基金：Support from the Max-Planck-Society and the LOEWE Research cluster SynChemBio is gratefully acknowledged.

语种：英文

外文关键词：cascade reactions; C-H activation; directed evolution; enantioselectivity; P450 monooxygenase

摘要：Biocatalytic cascade reactions using isolated stereoselective enzymes or whole cells in one-pot processes lead to value-added chiral products in a single workup. The concept has been restricted mainly to starting materials and intermediate products that are accepted by the respective wild-type enzymes. In the present study, we exploited directed evolution as a means to create E. coli whole cells for regio- and stereoselective cascade sequences that are not possible using man-made catalysts. The approach is illustrated using P450-BM3 in combination with appropriate alcohol dehydrogenases as catalysts in either two-, three-, or four-step cascade reactions starting from cyclohexane, cyclohexanol, or cyclohexanone, respectively, leading to either (R,R)-, (S,S)-, or meso-cyclo-hexane-1,2-diol. The one-pot conversion of cyclohexane into (R)- or (S)-2-hydroxycyclohexanone in the absence of ADH is also described.