More than just a halogenase: modification of fatty acyl moieties by a trifunctional metal enzyme

Sarah M. Pratter, Jakov Ivkovic, Ruth Birner-Gruenberger, Rolf Breinbauer, Klaus Zangger, Grit Daniela Straganz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The highly selective oxidative halogenations by non-heme iron and α-ketoglutarate-dependent enzymes are key reactions in the biosynthesis of lipopeptides, and often bestow valuable bioactivity to the metabolites. Here we present the first biochemical characterization of a putative fatty acyl halogenase, HctB, which is found in the hectochlorin biosynthetic pathway of Lyngbya majuscula. Its unprecedented three-domain structure, which includes an acyl carrier protein domain, allows self-contained conversion of the covalently tethered hexanoyl substrate. Structural analysis of the native product by 13C NMR reveals high regioselectivity but considerable catalytic promiscuity. This challenges the classification of HctB as a primary halogenase: along with the proposed dichlorination, HctB performs oxygenation and an unprecedented introduction of a vinyl-chloride moiety into the nonactivated carbon chain. The relaxed substrate specificity is discussed with reference to a molecular model of the enzyme–substrate complex. The results suggest that fatty acyl transformation at the metal center of HctB can bring about considerable structural diversity in the biosynthesis of lipopeptides.
Original languageEnglish
Pages (from-to)567-574
JournalChemBioChem
Volume15
Issue number4
DOIs
Publication statusPublished - 2014

Fields of Expertise

  • Human- & Biotechnology

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