Engineering Unspecific Peroxygenases for Enantioselective α‐Hydroxylation of β‐Ketoesters
Abstract
Abstract Unspecific peroxygenases (UPOs) are promising biocatalysts for selective oxyfunctionalization. Compared to cytochrome P450 enzymes (P450s), the catalytic potential of UPOs has been less investigated, largely due to their limited natural diversity and the challenges associated with their optimization through enzyme engineering. In this study, we engineered an UPO from Aspergillus niger ( Ani UPO) to catalyze the enantioselective α‐hydroxylation of β‐ketoesters, a valuable transformation yet to be realized in biocatalysis. Through enzyme engineering, two Ani UPO variants, Ani UPO‐M3 and Ani UPO‐M6, were developed to produce a wide range of enantioenriched α‐hydroxy‐β‐ketoesters, achieving up to 97% yield, 4140 total turnover number (TTN), and >99:1 enantiomeric ratio (er). The biocatalytic process operates under mild conditions and is scalable for preparative applications. This study broadens the catalytic repertoire of UPOs and enhances their potential for industrial applications.
Article Details
Authors (10)
Zhen‐Yu Wang
Shanghai Frontiers Science Center for Drug Target Identification and Delivery National Key Laboratory of Innovative Immunotherapy, and Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs School of Pharmaceutical Sciences Shanghai Jiao Tong University Shanghai China
Xin‐Yuan Ma
Key Laboratory of Drug‐Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant‐Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, Department of Biopharmaceutics, West China School of Pharmacy Sichuan University Chengdu 610041 China
Ying Wu
Yang Liu
Guang‐Xin Lin
Key Laboratory of Drug‐Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant‐Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, Department of Biopharmaceutics, West China School of Pharmacy Sichuan University Chengdu 610041 China
Xiao‐Qi Liu
Key Laboratory of Drug‐Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant‐Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, Department of Biopharmaceutics, West China School of Pharmacy Sichuan University Chengdu 610041 China
Chun Zhang
Peng Chen
Yongxiang Zheng
Department of Biopharmaceutics West China School of Pharmacy, Sichuan University No. 17 People's South Road Chengdu 610041 China
Zhi‐Jun Jia
Key Laboratory of Drug‐Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant‐Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, Department of Biopharmaceutics, West China School of Pharmacy Sichuan University Chengdu 610041 China