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Synthesis of Vibegron Enabled by a Ketoreductase Rationally Designed for High pH Dynamic Kinetic Reduction
Author(s) -
Xu Feng,
Kosjek Birgit,
Cabirol Fabien L.,
Chen Haibin,
Desmond Richard,
Park Jeonghan,
Gohel Anupam P.,
Collier Steven J.,
Smith Derek J.,
Liu Zhuqing,
Janey Jacob M.,
Chung John Y. L.,
Alvizo Oscar
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201802791
Subject(s) - chemistry , cofactor , reduction (mathematics) , combinatorial chemistry , enzyme , stereoselectivity , kinetic energy , organic chemistry , catalysis , physics , geometry , mathematics , quantum mechanics
Described here is an efficient stereoselective synthesis of vibegron enabled by an enzymatic dynamic kinetic reduction that proceeds in a high‐pH environment. To overcome enzyme performance limitations under these conditions, a ketoreductase was evolved by a computationally and structurally aided strategy to increase cofactor stability through tighter binding.