Enganando O Citocromo P450bm3: Catálise De Várias Transformações De Substratos Não Nativos Usando Moléculas-Traiçoeiras

Abstract

TRICKING CYTOCHROME P450BM3: CATALYSIS OF VARIOUS NON-NATIVE SUBSTRATE TRANSFORMATIONS USING DECOY MOLECULES. In order to accomplish a greener chemistry, enzymes, such as the fatty-acid hydroxylase cytochrome P450BM3, have garnered increasing attention as potential candidates for the development of potent biocatalysts in recent years. However, one of the biggest issues hampering the quick and efficient application of P450BM3 as a biocatalyst lies in its stringent substrate specificity. Consequently, diverse mutagenesis-based approaches have been successfully employed as a means to alter the substrate specificity of P450BM3, leading to the generation of a myriad of highly specialised mutant variants. Nevertheless, repeated exhaustive mutagenesis is a laborious process with no guarantee for success, thus, alternative methods to more easily alter the enzyme’s substrate specificity have become increasingly desirable. In recent years, decoy molecules, which possess the ability to deceive wild-type P450BM3 into hydroxylating a range of non-native substrates, have emerged as such a “simpler” alternative. Within this review, focus will be placed upon the process underlying the development of these decoy molecules, which will be discussed in great detail. Furthermore, a summary of recent developments pertaining to the potential applications of decoy molecules from the development of a whole-cell biocatalyst to their use in crystallography will be discussed.