The Power of Deception: Using Decoy Molecules to Manipulate P450BM3 Biotransformations

Abstract

Cytochrome P450BM3 is a haemoenzyme that catalyses the monooxygenation of unactivated CH bonds. In the absence of an appropriate substrate, however, P450BM3 remains in an inactive state and catalysis does not proceed. Traditionally, mutagenesis has been the mainstay technique employed to overcome this limitation, opening P450BM3 up for non-native substrate hydroxylations. This highlight review will discuss a different approach, wherein native substrate mimics (decoy molecules) are employed to trick P450BM3 into mistakenly hydroxylating non-native substrates. This decoy molecule system has the advantage that the wild-type enzyme can be utilised, and laborious mutagenesis can be avoided. Major developments from the first discovery of decoy molecules to the present day will be briefly covered herein.