Enzymatic synthesis of fluorinated compounds.

Xinkuan Cheng, Long Ma

Journal: Applied microbiology and biotechnology 2021;105(21-22):8033-8058

PMID: 34625820

Abstract

Fluorinated compounds are widely used in the fields of molecular imaging, pharmaceuticals, and materials. Fluorinated natural products in nature are rare, and the introduction of fluorine atoms into organic compound molecules can give these compounds new functions and make them have better performance. Therefore, the synthesis of fluorides has attracted more and more attention from biologists and chemists. Even so, achieving selective fluorination is still a huge challenge under mild conditions. In this review, the research progress of enzymatic synthesis of fluorinated compounds is summarized since 2015, including cytochrome P450 enzymes, aldolases, fluoroacetyl coenzyme A thioesterases, lipases, transaminases, reductive aminases, purine nucleoside phosphorylases, polyketide synthases, fluoroacetate dehalogenases, tyrosine phenol-lyases, glycosidases, fluorinases, and multienzyme system. Of all enzyme-catalyzed synthesis methods, the direct formation of the C-F bond by fluorinase is the most effective and promising method. The structure and catalytic mechanism of fluorinase are introduced to understand fluorobiochemistry. Furthermore, the distribution, applications, and future development trends of fluorinated compounds are also outlined. Hopefully, this review will help researchers to understand the significance of enzymatic methods for the synthesis of fluorinated compounds and find or create excellent fluoride synthase in future research.Key points• Fluorinated compounds are distributed in plants and microorganisms, and are used in imaging, medicine, materials science.• Enzyme catalysis is essential for the synthesis of fluorinated compounds.• The loop structure of fluorinase is the key to forming the C-F bond.

© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Address: State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Laboratory of Metabolic Control Fermentation Technology, College of Biotechnology, Tianjin University of Science & Technology, No. 29, Thirteenth Street, Binhai New District, Tianjin, 300457, China.; State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Laboratory of Metabolic Control Fermentation Technology, College of Biotechnology, Tianjin University of Science & Technology, No. 29, Thirteenth Street, Binhai New District, Tianjin, 300457, China. [email protected].
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