Highly regioselective hydroxylation of polydatin, a resveratrol glucoside, for one-step synthesis of astringin, a piceatannol glucoside, by P450 BM3

• Published in: Enzyme and microbial technology 2017-02, Vol.97, p.34-42
• Main Authors: Le, Thien-Kim, Jang, Hyun-Hee, Nguyen, Ha Thi Huong, Doan, Tiep Thi My, Lee, Ga-Young, Park, Ki Deok, Ahn, Taeho, Joung, Young Hee, Kang, Hyung-Sik, Yun, Chul-Ho
• Format: Article
• Language: English
• Subjects: (E)-Astringin; Amino Acid Substitution; Bacillus megaterium - enzymology; Bacillus megaterium - genetics; Bacterial CYP102A1; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biocatalysis; Biocatalyst; Biotechnology; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Glucosides - biosynthesis; Glucosides - chemistry; Glucosides - metabolism; Hydroxylation; Kinetics; Mutagenesis, Site-Directed; NADPH-Ferrihemoprotein Reductase - genetics; NADPH-Ferrihemoprotein Reductase - metabolism; Piceatannol; Protein Engineering; Regioselective C[sbnd]H hydroxylation; Resveratrol; Stilbenes - chemistry; Stilbenes - metabolism
• ISSN: 0141-0229; 1879-0909
• DOI: 10.1016/j.enzmictec.2016.11.003

[Display omitted] •A set of CYP102A1 mutants can catalyze regioselective hydroxylation of polydatin.•Major product of polydatin hydroxylation is astringin, a piceatannol glucoside.•An efficient enzymatic synthesis of astringin, a piceatannol glucoside, was developed. Enzymatic conversion of natural glycosides to their corresponding hydroxylated products using cytochromes P450 has significant advantages over synthetic chemistry and even enzyme-catalyzed glycosylation of chemicals. At present, the basic strategy for making glycosides of stilbenoid compounds is to use the glycosylation activity of enzymes, such as glycosyltransferases. Here, an efficient synthesis of a valuable (E)-astringin, a piceatannol glucoside, was developed using CYP102A1 via the highly regioselective C-3′ hydroxylation of polydatin, a resveratrol glucoside. (E)-astringin is a high added value compound found in plants and wine. Benzylic hydroxylation of polydatin provides an attractive route to (E)-astringin, a catechol product. Thus far, chemical and enzymatic methods of producing (E)-astringin have not been developed. In the present study, a set of CYP102A1 mutants from Bacillus megaterium was found to catalyze regioselective hydroxylation of polydatin at the C-3′ position to generate an (E)-astringin, a piceatannol glucoside.