Nucleocidin, a halogenated natural product made by Streptomyces calvus

If one were to choose a class of molecule that has done the most harm to the public perception of chemistry, ‘organohalogens’ would undoubtedly top the list. The halogens (fluorine, chlorine, bromine and iodine) are present in a variety of controversial man-made molecules, including dioxins (emissions from incinerators), PCB’s (electrical transformers), polyvinylchloride (PVC pipes), herbicides (the weed killer 2,4-D), and insecticides (DDT, which inspired Rachel Carson’s ‘Silent Spring’ and an entire environmental movement). What is less known is that organohalogens are not exclusively man-made or inherently toxic to the environment. In fact, nature also incorporates halogen atoms into a startling number and variety of molecules, with several thousand known to date. The chemical factories that churn out these natural organohalogens are typically bacteria living in the soil and ocean, although mammals (including humans), insects, plants, and sea sponges can also produce these molecules. Many of these naturally occurring organohalogens have useful anticancer, antibacterial and antifungal properties. The halogen is not merely decorative; these molecules often lose their useful bioactivities when the halogen substituent is removed. Dirt has been figuratively changed to gold, with soil-dwelling bacteria giving us life-saving organohalogens such as vancomycin (often the drug of last resort against antibiotic resistant bacteria) and chloramphenicol (one of the early ‘wonder drugs’ against typhus). Nature uses enzymes called ‘halogenases’ to install halogens in these molecules, and they do so with stunning region-control that chemists cannot easily replicate in the lab. Likewise, the halogenases operate in aqueous solution (~ pH 7) at room temperature and under ambient atmospheric conditions, which are considerably safer conditions than those used by chemists to perform halogenation reactions. Our lab is interested in characterizing the mechanisms of halogenases, as well as developing these enzymes into industrial biocatalysts.