The superfamily of cytochrome P450 enzymes is one of the most versatile biocatalyst systems in nature. P450 enzymes are capable of catalyzing more than 20 distinct types of reactions including regio- and stereoselective oxidation of inactivated C？H bonds (hydroxylation and epoxidation), dealkylation, C？C bond cleavage, aromatic coupling, and others. Recently, more novel activities such as decarboxylation, nitration, farnesene synthase activity, and carbene transfer have been reported, reflecting the ability to further diversify the function of these versatile enzymes. 

For almost all P450 enzymes, redox partner proteins are required for the electron transfer during catalysis. For practical purposes due to the difficulty of obtaining native partners, one or more surrogate redox partners, acting either in isolation or as artificially fused protein complexes, are often employed in functional characterization or synthetic applications of P450s. The behind assumption is that the choice of surrogate partners or their mode of action is not necessarily expected to affect the type and selectivity of reactions catalyzed by P450s. Although alternative redox partners may influence catalytic efficiency and/or product distribution, the chemical identity of products themselves is apparently determined by the P450 enzyme.  

However, an internationally collaborative team led by Professor LI Shengying of Enzyme Engineering Group (EEG) at Qingdao Institute of Bioenergy and Bioprocess Technology recently demonstrated solid evidence to challenge the above generally accepted “postulate”. During their study on MycG, which is the multifunctional P450 monooxygenase involved in the biosynthetic pathway of 16-membered ring macrolide mycinamicins in the rare actinomycete Micromonospora griseorubida, Dr. ZHANG Wei found that novel demethylated mycinamicin products were generated by P450 MycG supported by a stand-alone form of the RhFRED reductase domain, as opposed to RhFRED fused to MycG.

This finding highlights the larger potential role of variant redox partner protein？protein interactions in modulating the catalytic activity of P450 enzymes. This new discovery indicates that P450 enzymes could be even more versatile in vivo than previously considered, because these biocatalysts might interact with a variety of redox partners to gain alternative activities. This may impart evolutionary advantages to the host organisms through detoxifying a more diverse range of xenobiotics or synthesizing more secondary metabolites to adapt to ever-changing environments.