Engineering Tauriopine Dehydrogenase for Efficient Catalytic Synthesis of (R)‐Alpha‐Ethyl‐2‐Oxo‐1‐Pyrrolidineacetic Acid

Author:

Zhen Xin12,Feng XiSong3,Song Wei3,Wei Wanqing12,Wu Jing3,Wen Jian3,Hu Guipeng3,Li Xiaomin12,Gao Cong12,Chen Xiulai12,Liu Liming12ORCID

Affiliation:

1. School of Biotechnology Jiangnan University Wuxi 214122 China

2. Key Laboratory of Industrial Biotechnology of Ministry of Education Jiangnan University Wuxi 214122 China

3. School of Life Sciences and Health Engineering Jiangnan University Wuxi 214122 China

Abstract

AbstractThe synthetic pathway for Etiracetam depends on alpha‐ethyl‐2‐oxo‐1‐pyrrolidineacetic acid (AEOPA) as a crucial intermediate. This paper presents an enzymatic synthesis approach for producing (R)‐AEOPA. Through database mining, we discovered a tauriopine dehydrogenase capable of catalyzing the reaction between γ‐aminobutyric acid and 2‐oxobutyric acid, resulting in the synthesis of (R)‐4‐(carboxypropylamino) butyric acid with a specific activity of 6.74 U/mg. By enhancing substrate affinity and catalytic efficiency of CgTaDH through protein engineering, we achieved a 5.9‐fold increase in enzyme activity compared to the wild type. Further optimization led to a space‐time yield (STY) of 3.95 g/L/h for (R)‐4‐(carboxypropyl amino) butyric acid and a high yield of 73.0 % for the final product, (R)‐AEOPA. This study demonstrates a novel synthesis method for (R)‐AEOPA and highlights the potential of biocatalysis in improving the production of Etiracetam through successful enzymatic processes.

Publisher

Wiley

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