| Autor: |
Williams IS; Leicester School of Pharmacy, De Montfort University , Leicester, LE1 9BH, United Kingdom.; CYP Design Limited, Innovation Centre , 49 Oxford Street, Leicester, LE1 5XY, United Kingdom., Chib S; Fermentation Technology Division, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu-180001, India., Nuthakki VK; Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu-180001, India., Gatchie L; Leicester School of Pharmacy, De Montfort University , Leicester, LE1 9BH, United Kingdom.; CYP Design Limited, Innovation Centre , 49 Oxford Street, Leicester, LE1 5XY, United Kingdom., Joshi P; Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu-180001, India., Narkhede NA; Instrumentation Division, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu-180001, India., Vishwakarma RA; Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu-180001, India., Bharate SB; Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu-180001, India.; Academy of Scientific & Innovative Research (AcSIR), CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu-180001, India., Saran S; Fermentation Technology Division, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu-180001, India., Chaudhuri B; Leicester School of Pharmacy, De Montfort University , Leicester, LE1 9BH, United Kingdom.; CYP Design Limited, Innovation Centre , 49 Oxford Street, Leicester, LE1 5XY, United Kingdom. |
| Abstrakt: |
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. |
