Department of Process Research and Development, MRL, Merck & Co., Inc., Rahway, NJ, 07065, USA.
Codexis, Inc., 200 Penobscot Drive, Redwood City, CA, 94063, USA.
Angew Chem Int Ed Engl. 2018 Jun 4;57(23):6863-6867. doi: 10.1002/anie.201802791. Epub 2018 May 3.
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.
本文描述了一种通过酶促动态动力学还原实现的高效立体选择性合成 vibegron 的方法，该反应在高 pH 环境中进行。为了克服这些条件下酶性能的限制，通过计算和结构辅助策略对酮还原酶进行了进化，通过更紧密的结合来提高辅因子的稳定性。
