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May 16, 2018

Synthesis of Vibegron Enabled by a Ketoreductase Rationally Designed for High pH Dynamic Kinetic Reduction

Codexis Authors:
Dr. Fabien L. Cabirol, Dr. Haibin Chen, Anupam P. Gohel, Dr. Steven J. Collier, Dr. Derek J. Smith, Dr. Oscar Alvizo

All Authors:
Dr. Feng Xu, Dr. Birgit Kosjek,  Richard Desmond, Dr. Jeonghan Park,  Dr. Zhuqing Liu, Dr. Jacob M. Janey,  Dr. John Y. L. Chung

Abstract:
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.

Full article published in Angewandte Chemie

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