Journal
ENZYME AND MICROBIAL TECHNOLOGY
Volume 126, Issue -, Pages 77-85Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.enzmictec.2019.04.001
Keywords
Aldo-keto reductase; (R)-Pantolactone; Ketopantolactone; Asymmetric reduction; Catalytic mechanism
Categories
Funding
- Natural Science Foundation of Zhejiang Province [LY15B060011, LQ12B06007]
- China Postdoctoral Science Foundation [2016M601966]
- National Natural Science Foundation of China [21406201, 21206024]
- Hangzhou Science and Technology Project [20130533B17, 20151232I34]
Ask authors/readers for more resources
(R)-pantolactone is a key chiral intermediate for synthesizing calcium (R)-pantothenate. The commercial synthesis of (R)-pantolactone is performed through the resolution of racemic pantolactone using lactonase-catalyzed enantioselective hydrolysis. The process needs highly toxic hydrogen cyanide and a tedious dynamic kinetic resolution. In this study, we investigated an alternative method to prepare (R)-pantolactone through asymmetric reduction of ketopantolactone (KPL). An NADPH-dependent conjugated polyketone reductase gene from Candida dubliniensis CD36 (CduCPR) was functionally overexpressed in Escherichia coil BL21 (DE3). Recombinant CduCPR belonged to the aldo-keto reductase superfamily, and showed high catalytic activity and stereoselectivity using KPL as the substrate. In a continuous feeding reaction, 200 mM ketopantolactone was reduced to (R)-pantolactone with 98% conversion and 99% enantiomeric excess (e.e.) within 2.0 h. The catalytic mechanism was further investigated. Tyr66 functions as a proton donor following hydrogen transfer from NADPH. Thr30 and His128 are critical residues to bind and orient KPL. Therefore, the recombinant CduCPR from C. dubliniensis exhibited potential application in the asymmetric synthesis of (R)-pantolactone.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available