Biotransformation of Chrysin to Baicalein: Selective C6-Hydroxylation of 5,7-Dihydroxyflavone Using Whole Yeast Cells Stably Expressing Human CYP1A1 Enzyme

Bharate, Sandip B.; Nuthakki, Vijay K.; Williams, Ibidapo S.; Chib, Shifali; Gatchie, Linda; Joshi, Prashant; Narkhede, Niteen A.; Vishwakarma, Ram A.; Saran, Saurabh; Chaudhuri, Bhabatosh

Abstract

© 2017 American Chemical Society. Naturally occurring polyphenolic compounds are of medicinal importance because of their unique antioxidant, anticancer, and chemopreventive properties. Baicalein, a naturally occurring polyhydroxy flavonoid possessing a diverse range of pharmacological activities, has been used in traditional medicines for treatment of various ailments. Apart from its isolation from natural sources, its synthesis has been reported via multistep chemical approaches. Here, we report a preparative-scale biotransformation, using whole yeast cells stably expressing human cytochrome P450 1A1 (CYP1A1) enzyme that allows regioselective C6-hydroxylation of 5,7-dihydroxyflavone (chrysin) to form 5,6,7-trihydroxyflavone (baicalein). Molecular modeling reveals why chrysin undergoes such specific hydroxylation mediated by CYP1A1. More than 92% reaction completion was obtained using a shake-flask based process that mimics fed-batch fermentation. Such highly efficient selective hydroxylation, using recombinant yeast cells, has not been reported earlier. Similar CYP-expressing yeast cell based systems are likely to have wider applications in the syntheses of medicinally important polyphenolic compounds.

Citation

Bharate, S. B., Nuthakki, V. K., Williams, I. S., Chib, S., Gatchie, L., Joshi, P., …Chaudhuri, B. (2017). Biotransformation of Chrysin to Baicalein: Selective C6-Hydroxylation of 5,7-Dihydroxyflavone Using Whole Yeast Cells Stably Expressing Human CYP1A1 Enzyme. Journal of Agricultural and Food Chemistry, 65(34), 7440-7446. https://doi.org/10.1021/acs.jafc.7b02690

• Journal Article Type: Article
• Acceptance Date: Aug 7, 2017
• Publication Date: Aug 30, 2017
• Deposit Date: May 9, 2018
• Publicly Available Date: Aug 7, 2018
• Journal: Journal of Agricultural and Food Chemistry
• Print ISSN: 0021-8561
• Electronic ISSN: 1520-5118
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 65
• Issue: 34
• Pages: 7440-7446
• DOI: https://doi.org/10.1021/acs.jafc.7b02690
• Keywords: baicalein, biotransformation, chrysin, CYP1A1, hydroxylation, yeast cells
• Public URL: https://uwe-repository.worktribe.com/output/883199
• Publisher URL: http://dx.doi.org/10.1021/acs.jafc.7b02690
• Related Public URLs: https://pubs.acs.org/doi/10.1021/acs.jafc.7b02690
• Additional Information: Additional Information : This is the accepted version of the article. the final version can be found at: http://dx.doi.org/10.1021/acs.jafc.7b02690