文献类型：期刊文献

英文题名：Design of a self-sufficient hydride-shuttling cascade for concurrent bioproduction of 7,12-dioxolithocholate and l-tert-leucine

作者：You, Zhi-Neng[1];Zhou, Ke[1];Han, Yu[1];Yang, Bing-Yi[1];Chen, Qi[1];Pan, Jiang[1];Qian, Xiao-Long[1,2];Li, Chun-Xiu[1];Xu, Jian-He[1]

机构：[1]East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg, State Key Lab Bioreactor Engn, Lab Biocatalysis & Synthet Biotechnol, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Suzhou Bioforany Enzynch Co Ltd, 8 Yanjiuyuan Rd, Changshu 215512, Jiangsu, Peoples R China

年份：2021

卷号：23

期号：11

起止页码：4125

外文期刊名：GREEN CHEMISTRY

收录：;EI(收录号：20212410512247);WOS:【SCI-EXPANDED(收录号:WOS:000651842100001)】；

基金：This work was financially supported by The National Key Research and Development Program of China (No. 2018YFC1706200 and 2019YFA09005000), The National Natural Science Foundation of China (No. 31971381, 21871085, and 21536004), and the Fundamental Research Funds for the Central Universities (No. 22221818014).

语种：英文

外文关键词：Amines - Cost effectiveness - Hydrides

摘要：Oxidoreductase-mediated biotransformation often requires consumption of a secondary sacrificial co-substrate and an additional auxiliary enzyme to drive the cofactor regeneration, which results in generation of unwanted by-product. Herein, we report a highly atom-economic self-sufficient hydride-shuttling cascade to concurrently obtain two pharmaceutically important building blocks (7,12-dioxo-lithocholic acid and l-tert-leucine) in which oxidation of cholic acid (CA) and reductive amination of trimethylpyruvic acid were integrated for redox self-recycling. In this cascade, the cofactor acts as a hydride shuttle that interconnects the two synthetically relevant reactions at the cost of only inorganic ammonium as the sacrificial agent and generates water as the greenest by-product. The preparative biotransformation using a whole-cell biocatalyst in the absence of any exogenous cofactor displayed a space-time yield of 768 g L-1 d(-1) and a total turnover number (TTN) of 20 363 for NAD(+) recycling. This represents the highest cofactor TTN reported to date for the bio-oxidation of CA, indicating the great potential of this cofactor and redox self-sufficient bioprocess for cost-effective and sustainable biomanufacturing of high-value-added products.