A set of closely related methyltransferases for site-specific tailoring of anthraquinone pigments

Eva M. Huber, Lukas Kreling, Antje K. Heinrich, Maximilian Dünnebacke, Alexander Pöthig, Helge B. Bode, Michael Groll

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Modification of the polyketide anthraquinone AQ-256 in the entomopathogenic Photorhabdus luminescens involves several O-methylations, but the biosynthetic gene cluster antA-I lacks corresponding tailoring enzymes. We here describe the identification of five putative, highly homologous O-methyltransferases encoded in the genome of P. luminescens. Activity assays in vitro and deletion experiments in vivo revealed that three of them account for anthraquinone tailoring by producing three monomethylated and two dimethylated species of AQ-256. X-ray structures of all five enzymes indicate high structural and mechanistic similarity. As confirmed by structure-based mutagenesis, a conserved histidine at the active site likely functions as a general base for substrate deprotonation and subsequent methyl transfer in all enzymes. Eight complex structures with AQ-256 as well as mono- and dimethylated derivatives confirm the substrate specificity patterns found in vitro and visualize how single amino acid differences in the active-site pockets impact substrate orientation and govern site-specific methylation.

Original languageEnglish
Pages (from-to)573-583.e5
JournalStructure
Volume31
Issue number5
DOIs
StatePublished - 4 May 2023

Keywords

  • Photorhabdus luminescens
  • X-ray crystallography
  • anthraquinone
  • methyl transfer
  • natural product biosynthesis

Fingerprint

Dive into the research topics of 'A set of closely related methyltransferases for site-specific tailoring of anthraquinone pigments'. Together they form a unique fingerprint.

Cite this