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Enzymatic Halogenation
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.
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