Nature's Inventory of Halogenation Catalysts:  Oxidative Strategies Predominate

Halogenated molecules are widely distributed in the biosphere. A variety of halogenated aromatic and aliphatic compounds are man-made and can be harmful to the environment due to their slow rates of biodegradation.1 Halogenated organic molecules can also arise as natural products in which the carbon−halogen bonds are generated enzymatically. To date, more than 4500 halogenated natural products have been discovered,2 though it is likely to be a substantially incomplete inventory. Enzymatic incorporation of halogens during natural product assembly alters physical properties, including electronic and steric effects that can be consequential for determining the affinity and selectivity of interactions with biological targets. Many of the genes encoding such halogen-incorporating enzymes are embedded in specific biosynthetic gene clusters, enabling coordinate regulation to activate these secondary metabolite pathways.