文献类型：期刊文献

英文题名：A green-by-design system for efficient bio-oxidation of an unnatural hexapyranose into chiral lactone for building statin side-chains

作者：Jiao, Xue-Cheng;Zhang, Yu-Jun;Chen, Qi;Pan, Jiang[1];Xu, Jian-He[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China; East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg, Shanghai 200237, Peoples R China

年份：2016

卷号：6

期号：19

起止页码：7094

外文期刊名：CATALYSIS SCIENCE & TECHNOLOGY

收录：;EI(收录号：20164102879128);WOS:【SCI-EXPANDED(收录号:WOS:000384876400011)】；

基金：This work was financially supported by the National Natural Science Foundation of China (No. 21276082, 21505044 & 21536004), Ministry of Science and Technology (No. 2012AA022201D), and Ministry of Education (222201414039), P.R. China.

语种：英文

外文关键词：Product design - Chains - Oxidation - Catalyst activity - Reaction intermediates

摘要：A novel NADP+-dependent aldehyde dehydrogenase (LeADH) was identified from Lodderomyces elongisporus and engineered for bio-oxidation of (3R, 5S)-6-chloro-2,4,6-trideoxy-erythro-hexapyranose, a key chiral intermediate, for synthesis of statin side-chains. The catalytic activity of LeADH was improved by 12-fold through the combinatorial active-site saturation test (CAST) strategy. The resultant variant, LeADH(I87F/N235H/P236H), was co-expressed with an NADPH oxidase SmNOXV193R/V194H in Escherichia coli. A green-by-design system was then constructed for efficient oxidation of the unnatural hexapyranose into the key statin side chain, (3R, 5S)-6-chloro-2,4,6-trideoxy-erythro-hexonolactone, with oxygen as the co-substrate and water as the sole by-product.