title: New reactions and products resulting from alternative interactions between the P450 enzyme and redox partners.
abstract: Cytochrome P450 enzymes are capable of catalyzing a great variety of synthetically useful reactions such as selective C-H 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-protein interactions in modulating the catalytic activity of P450 enzymes.
authors: CAS Key Laboratory of Biofuels, and Shandong Provincial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences , Qingdao, Shandong 266101, China.
authors: Wei
authors: W
authors: Zhang
authors: Yi
authors: Y
authors: Liu
authors: Jinyong
authors: J
authors: Yan
authors: Shaona
authors: S
authors: Cao
authors: Fali
authors: F
authors: Bai
authors: Ying
authors: Y
authors: Yang
authors: Shaohua
authors: S
authors: Huang
authors: Lishan
authors: L
authors: Yao
authors: Yojiro
authors: Y
authors: Anzai
authors: Fumio
authors: F
authors: Kato
authors: Larissa M
authors: LM
authors: Podust
authors: David H
authors: DH
authors: Sherman
authors: Shengying
authors: S
authors: Li
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D020134:Catalytic Domain; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism*; D018942:Macrolides / Q000378:metabolism; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011485:Protein Binding
chemical_list: D001426:Bacterial Proteins; D018942:Macrolides; C577531:MycG protein, Micromonospora; C026686:mycinamicins; D003577:Cytochrome P-450 Enzyme System