Development of a multi-enzymatic desymmetrization and its application for the biosynthesis of L-norvaline from DL-norvaline

作者：Qi, Yunlong; Yang, Taowei^*; Zhou, Junping; Zheng, Junxian; Xu, Meijuan; Zhang, Xian; Rao, Zhiming^*; Yang, Shang-Tian

来源：Process Biochemistry, 2017, 55: 104-109.

DOI：10.1016/j.procbio.2017.01.022

• Desymmetrization
• D-Amino acid oxidase
• Leucine dehydrogenase
• NADH regeneration

Perindopril is an effective antihypertensive drug in strong demand used to treat hypertension. L-norvaline is a vital intermediate of Perindopril production mainly produced by chemical synthesis with low purity. We developed an environmentally friendly method to produce L-norvaline with high purity based on a desymmetrization process. D-Norvaline was oxidized to the corresponding keto acid by D-amino acid oxidase from the substrate DL-norvaline. Asymmetric hydrogenation of the keto acid to L-norvaline was carried out by leucine dehydrogenase with concomitant oxidation of NADH to NAM A NADH regeneration system was introduced by overexpressing a formate dehydrogenase. The unwanted H2O2 by-product generated during D-norvaline oxidation was removed by adding catalase. A total of 54.09 g/L of L-norvaline was achieved, with an enantiomeric excess over 99% under optimal conditions, with a 96.7% conversion rate. Our desymmetrization method provides an environmental friendly strategy for the production of enantiomerically pure L-norvaline in the pharmaceutical industry.

• 出版日期2017-4
• 单位江南大学