Mechanistic Insights into Interactions between Bacterial Class I P450 Enzymes and Redox Partners

By L. Du, Fengwei Li, Xingwang Zhang, Z. Qu, Lei Han, Zhong Li, Jingran Sun, F. Qi, Qiuping Yao, Yue Sun and 2 more. ACS Catalysis, 2018

88 citations recorded by the source corpus.

Cytochrome P450 enzymes are highly diversified biocatalysts associated with steroid biosynthesis, xenobiotic metabolism, biosynthesis of natural products, and industrial oxidation reactions. A typical P450 catalytic cycle requires sequential transfer of two electrons from NAD(P)H to the heme-iron reactive center for O2 activation. For the most abundant bacterial Class I P450 systems, this important process is usually mediated by two redox partner proteins including an FAD-containing ferredoxin reductase (FdR) and a small iron–sulfur protein, ferredoxin (Fdx). However, it is often unclear which pair of Fdx and FdR among multiple redox partners is the optimal one for a specific Class I P450 enzyme. To address this important but underexplored question, herein, a reaction matrix network with 16 Fdxs, 8 FdRs, and 6 P450s (against 7 substrates) was constituted. By analyzing the reactivity profiles of 896 P450 reactions, together with phylogenetic analysis, redox potential measurements, structural simulations, a...

Subfields: Inorganic Chemistry, Molecular Biology, Pharmacology

View Paper: https://www.semanticscholar.org/paper/d7e991237aadb3454a387c2cd52fbdc218433fe5