Open AccessA flavin-dependent halogenase catalyzes the chlorination step in the biosynthesis of Dictyostelium differentiation-inducing factor 1
Author(s) -
Christopher S. Neumann,
Christopher T. Walsh,
Robert R. Kay
Publication year - 2010
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1001681107
Subject(s) - dictyostelium discoideum , biology , flavin group , myxococcus xanthus , dictyostelium , biosynthesis , transformation (genetics) , biochemistry , myxobacteria , gene , enzyme , genetics , bacteria , mutant
Differentiation-inducing factor 1 (DIF-1) is a polyketide-derived morphogen which drives stalk cell formation in the developmental cycle ofDictyostelium discoideum . Previous experiments demonstrated that the biosynthetic pathway proceeds via dichlorination of the precursor molecule THPH, but the enzyme responsible for this transformation has eluded characterization. Our recent studies on prokaryotic flavin-dependent halogenases and insights from the sequencedDd genome led us to a candidate gene for this transformation. In this work, we present in vivo and in vitro evidence thatchlA fromDd encodes a flavin-dependent halogenase capable of catalyzing both chlorinations in the biosynthesis of DIF-1. The results provide in vitro characterization of a eukaryotic oxygen-dependent halogenase and demonstrate a broad reach in biology for this molecular tailoring strategy, notably its involvement in the differentiation program of a social amoeba.