Halogenated organic compounds pervade chemistry, playing important roles as industrial, agrochemical, and pharmaceutical products, as well as functioning as essential building blocks and intermediates in organic synthesis. Common halogenation methods often involve activated starting materials and multistep functional group conversion sequences that produce wasteful and toxic by-products. For example, arene halogenation via electrophilic aromatic substitution requires harsh reaction conditions and stoichiometric reagents and often proceeds with poor regioselectivity. The flavin dependent halogenase RebH, on the other hand, chlorinates and brominates tryptophan with high selectivity under ambient conditions using chloride/bromide as a halogen source and O2 as a terminal oxidant. I will discuss efforts from my group involving the evolution of RebH variants with improved stability, expanded substrate scope, and altered site selectivity. More recent efforts involving additional flavin dependent halogenases, genome mining, late stage halogenation, and substrate activity profiling will also be covered. Finally, extension of our efforts to aliphatic halogenation will be discussed.

Engineering halogenases for sp2 and sp3 C-H halogenation

256th National Meeting (2018)

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