New Reactions and Products Resulting from Alternative Interactions between the P450 Enzyme and Redox Partners

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• 作者：Wei Zhang ; Yi Liu ; Jinyong Yan ; Shaona Cao ; Fali Bai ; Ying Yang ; Shaohua Huang ; Lishan Yao ; Yojiro Anzai ; Fumio Kato ; Larissa M. Podust ; David H. Sherman ; Shengying Li
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：March 5, 2014
• 年：2014
• 卷：136
• 期：9
• 页码：3640-3646
• 全文大小：412K
• 年卷期：v.136,no.9(March 5, 2014)
• ISSN：1520-5126

文摘

Cytochrome P450 enzymes are capable of catalyzing a great variety of synthetically useful reactions such as selective C鈥揌 functionalization. Surrogate redox partners are widely used for reconstitution of P450 activity based on the assumption that the choice of these auxiliary proteins or their mode of action does not affect the type and selectivity of reactions catalyzed by P450s. Herein, we present an exceptional example to challenge this postulate. MycG, a multifunctional biosynthetic P450 monooxygenase responsible for hydroxylation and epoxidation of 16-membered ring macrolide mycinamicins, is shown to catalyze the unnatural N-demethylation(s) of a range of mycinamicin substrates when partnered with the free Rhodococcus reductase domain RhFRED or the engineered Rhodococcus-spinach hybrid reductase RhFRED-Fdx. By contrast, MycG fused with the RhFRED or RhFRED-Fdx reductase domain mediates only physiological oxidations. This finding highlights the larger potential role of variant redox partner protein鈥損rotein interactions in modulating the catalytic activity of P450 enzymes.