Roles of the Synergistic Reductive O-Methyltransferase GilM and of O-Methyltransferase GilMT in the Gilvocarcin Biosynthetic Pathway

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• 作者：Nidhi Tibrewal ; Theresa E. Downey ; Steven G. Van Lanen ; Ehesan Ul Sharif ; George A. O鈥橠oherty ; J眉rgen Rohr
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：August 1, 2012
• 年：2012
• 卷：134
• 期：30
• 页码：12402-12405
• 全文大小：257K
• 年卷期：v.134,no.30(August 1, 2012)
• ISSN：1520-5126

文摘

Two enzymes of the gilvocarcin biosynthetic pathway, GilMT and GilM, with unclear functions were investigated by in vitro studies using purified, recombinant enzymes along with synthetically prepared intermediates. The studies revealed GilMT as a typical S-adenosylmethionine (SAM) dependent O-methyltransferase, but GilM was identified as a pivotal enzyme in the pathway that exhibits dual functionality in that it catalyzes a reduction of a quinone intermediate to a hydroquinone, which goes hand-in-hand with a stabilizing O-methylation and a hemiacetal formation. GilM mediates its reductive catalysis through the aid of GilR that provides FADH₂ for the GilM reaction, through which FAD is regenerated for the next catalytic cycle. This unusual synergy eventually completes the biosynthesis of the polyketide-derived defuco-gilvocarcin chromphore.