The X‐Ray Crystal Structure of BorF , the Flavin Reductase Subunit of a Two‐Component Flavin‐Dependent Tryptophan Halogenase

BorF is a short-chain flavin reductase from a desert soil bacterium that uses NADH to reduce FAD to FADH₂, which is used by the tryptophan-6-halogenase BorH to chlorinate tryptophan in the biosynthetic pathway of borregomycin A. The X-ray crystal structure of BorF bound to FAD was solved to 2.37 Å by molecular replacement. It consists of a homodimer of single-domain protomers, each with a Greek key split β-barrel topology containing a domain-swapped N-terminal α-helix, as previously seen in homologous proteins. Insertions and deletions in the region between α3 and β5 result in different conformations of the adenosine portion of FAD bound to BorF and structurally related reductases. Comparison of the FAD-bound structures of BorF and BorH suggests that FAD must completely dissociate from BorH in order to be reduced by BorF.