Recent Advances in Synthetic Application and Engineering of Halogenases

Halogenating enzymes are able to introduce halogen substituents under ambient conditions using non-hazardous reagents with intriguing selectivity, which is highly desired in green chemistry. Although C-H functionalization such as halogenation is a well-known transformation in synthetic chemistry, the selective incorporation of halogens using conventional chemical approaches often remains challenging. Therefore, enzyme-based strategies have been emerging as valuable alternatives in recent years. Inspired by manifold developments of enzymatic halogenation, this review focuses on advances of halogenating enzymes and their application with particular emphasis on FAD-dependent halogenases (FDHs). Catalytic strategies, application scope and engineering of FDHs are outlined pointing to the increasing utility of halogenases as promising biocatalysts. Current limitations as well as potential future developments of their synthetic utility are being discussed.