Nature Communications (Jan 2021)

Thioesterase-mediated side chain transesterification generates potent Gq signaling inhibitor FR900359

  • Cornelia Hermes,
  • René Richarz,
  • Daniel A. Wirtz,
  • Julian Patt,
  • Wiebke Hanke,
  • Stefan Kehraus,
  • Jan Hendrik Voß,
  • Jim Küppers,
  • Tsubasa Ohbayashi,
  • Vigneshwaran Namasivayam,
  • Judith Alenfelder,
  • Asuka Inoue,
  • Peter Mergaert,
  • Michael Gütschow,
  • Christa E. Müller,
  • Evi Kostenis,
  • Gabriele M. König,
  • Max Crüsemann

DOI
https://doi.org/10.1038/s41467-020-20418-3
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 12

Abstract

Read online

FR900359 (FR) is a Gq protein inhibitor depsipeptide isolated from an uncultivable plant endosymbiont and synthesized by non-ribosomal peptide synthetases. Here, the authors discover a cultivable bacterial FR producer and show that FrsA thioesterase domain catalyses intermolecular transesterification of the FR side chain to the depsipeptide core during biosynthesis, improving Gq inhibition properties.