Halogenases for the synthesis of small molecules

Enzymatic halogenation is a rapidly developing tool in the synthetic chemist's toolbox. Utilizing oxygen, halide salts and operating at ambient temperatures in aqueous media, halogenating enzymes, particularly flavin- or Fe(II)/α-ketoglutarate dependent halogenases, allow the regio- and stereoselective installation of halogen atoms to yield valuable building blocks and uniquely derivatized complex molecules, including natural products. Apart from modulating the physico-chemical properties of molecules and, in consequence, their biological activity, halogen atoms can also serve as chemical linchpins for further derivatization of the molecular scaffold, for example in chemo-enzymatic cascades. Thanks to rapid advances in bioinformatic enzyme sourcing, biosynthetic pathway elucidation and enzyme engineering strategies, the palette of enzymatically produced halogenated structures is constantly growing. In addition, successful studies to improve catalytic performance of the halogenation biocatalysts are boding well for industrial applications.