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January 16, 2020

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

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.


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