Peptidic Tryptophan Halogenation by a Promiscuous Flavin-Dependent Enzyme.

ABSTRACT: Amino acids undergo numerous enzymatic modifications. However, the broad applicability of amino acid-modifying enzymes for synthetic purposes is limited by narrow substrate scope and often unknown regulatory or accessory factor requirements. Here, we characterize ChlH, a flavin-dependent halogenase (FDH) from the chlorolassin biosynthetic gene cluster. Unlike characterized peptide-modifying FDHs, which are limited to either specifically modified peptides or the termini of linear peptides, ChlH halogenates internal Trp residues of linear peptides, as well as N- and C-terminal Trp. Scanning mutagenesis of the substrate peptide ChlA revealed Trp was tolerated by ChlH at nearly every position. Molecular dynamics simulations corroborated the importance of a C-terminal motif in ChlA and provided

SUBMITTER: Rice AJ 

PROVIDER: S-EPMC12518702 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature