Scheme 2. FDH-mediated electrophilic halogenation. (A) Biocatalytic cycle of a flavin-dependent halogenase, showing the release of hypohalous acid. HOX is channelled through a ∼10 Å tunnel. The regioselectivity of the electrophilic aromatic substitution is postulated to be achieved by: (B) a lysine residue, at the end of the tunnel that reacts with HOX to form a haloamine intermediate,43 and (C) lysine and glutamine, acting in concert to position HOX and further electronically activate the tryptophan.39 (D) Extrapolation of the crystal structure of PrnA showing how Lys79 is positioned over C7 of the indole ring mediating regioselective halogenation.
