Bioresource Technology 249 (2018) 161–167 Contents lists available at ScienceDirect Bioresource Technology journal homepage: www.elsevier.com/locate/biortech Biosynthesis of tert-butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate by carbonyl reductase from Rhodosporidium toruloides in mono and biphasic media Zhi-Qiang Liu, Lin Wu, Ling Zheng, Wen-Zhong Wang, Xiao-Jian Zhang, Li-Qun Jin, Yu-Guo Zheng Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China GR APHICAL A BSTRACT ARTICLE I NFO ABSTRACT Keywords: tert-Butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate ((3R,5S)-CDHH) is the key intermediate for synthesis of tert-butyl (S)-6-chloro-5-hydroxy-3- atorvastatin and rosuvastatin. Carbonyl reductase exhibits excellent activity toward tert-butyl (S)-6-chloro-5- oxohexanoate hydroxy-3-oxohexanoate ((S)-CHOH) to synthesize (3R,5S)-CDHH. In this study, a whole cell biosynthesis re- tert-butyl (3R,5S)-6-chloro-3,5- action system to produce (3R,5S)-CDHH was constructed in organic solvents. A solution of 10% (v/v) Tween-80 dihydroxyhexanoate was introduced to the reaction system as a co-solvent, which greatly enhanced biotransformation process, giving Carbonyl reductase 98.9% yield, > 99% ee and 1.8-fold higher space time yield in 5 h bioconversion of 1 M (S)-CHOH, compared Biphasic reaction system with 98.7% yield and > 99% ee in 9 h bioconversion of a purely aqueous reaction system. Moreover, a water- octanol biphasic reaction system was built and 20% of octanol
Heart & Lung: The Journal of Acute and Critical Care – Elsevier
Published: Nov 1, 2018
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