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Synthesis 2024; 56(04): 567-572
DOI: 10.1055/a-2076-9792
special topic
Synthetic Development of Key Intermediates and Active Pharmaceutical Ingredients (APIs)

Biocatalytic Synthesis of Chiral Benzylic Alcohols via Enantioselective Hydroxylation by a Self-Sufficient Cytochrome P450 from Deinococcus gobiensis

Hai-Bo Cui
a   Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi, 563000, P. R. of China
b   Key Laboratory of Basic Pharmacology of Ministry of Education, and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563000, P. R. of China
,
Ting Ma
a   Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi, 563000, P. R. of China
b   Key Laboratory of Basic Pharmacology of Ministry of Education, and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563000, P. R. of China
,
Ru-Yue Zhang
a   Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi, 563000, P. R. of China
b   Key Laboratory of Basic Pharmacology of Ministry of Education, and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563000, P. R. of China
,
Jing Shan
a   Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi, 563000, P. R. of China
b   Key Laboratory of Basic Pharmacology of Ministry of Education, and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563000, P. R. of China
,
Zhong-Qiang Wang
a   Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi, 563000, P. R. of China
b   Key Laboratory of Basic Pharmacology of Ministry of Education, and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563000, P. R. of China
,
Mei Bai
a   Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi, 563000, P. R. of China
b   Key Laboratory of Basic Pharmacology of Ministry of Education, and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563000, P. R. of China
,
Yong-Zheng Chen∗
a   Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi, 563000, P. R. of China
b   Key Laboratory of Basic Pharmacology of Ministry of Education, and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563000, P. R. of China
› Author AffiliationsWe are grateful for financial support from the National Natural Science Foundation of China (Nos. 21961048 and 32271537), the Guizhou Education Department Youth Science and Technology Talents Growth Project (QKHKY-2017-195), and the Science and Technology Department of Zunyi (ZSKH-2018-3, ZSKRPT-2020-5, and ZSKRPT-2021-5).
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Abstract

Enzymatic asymmetric benzylic hydroxylation represents a green synthesis of valuable chiral benzylic alcohols. The stereoselective C–H direct hydroxylation profile possessed by cytochrome P450 monooxygenases (P450s) makes it more attractive. Here, we successfully expressed a self-sufficient cytochrome P450 monooxygenase from Deinococcus gobiensis in Escherichia coli BL21(DE3) host. The recombinant E. coli (P450DG) strain performed well in terms of functionality and has stereoselective benzylic hydroxylation ability for propylbenzene substrates. Asymmetric benzylic hydroxylation of various aromatic compounds was further investigated using the recombinant E. coli (P450DG) strain based on the optimal conditions, producing the corresponding enantioenriched pharmaceutically relevant benzylic alcohols in moderate yields with good to excellent enantioselectivity.

Key words

biocatalysis - cytochrome P450 - enantioselective hydroxylation - whole-cell bioconversion - chiral benzylic alcohols

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2076-9792.
  • Supporting Information


Publication History

Received: 24 February 2023

Accepted after revision: 19 April 2023

Accepted Manuscript online:
19 April 2023

Article published online:
23 May 2023

© 2024. Thieme. All rights reserved

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