Genome Mining of a Fungal Polyketide Synthase-Nonribosomal Peptide Synthetase Hybrid Megasynthetase Pathway to Synthesize a Phytotoxic N-Acyl Amino Acid

Org Lett. 2024 May 3;26(17):3597-3601. doi: 10.1021/acs.orglett.4c01039. Epub 2024 Apr 25.

Abstract

Guided by the retrobiosynthesis hypothesis, we characterized a fungal polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrid megasynthetase pathway to generate 2-trans-4-trans-2-methylsorbyl-d-leucine (1), a polyketide amino acid conjugate that inhibits Arabidopsis root growth. The biosynthesis of 1 includes a PKS-NRPS enzyme to assemble an N-acyl amino alcohol intermediate, which is further oxidized to an N-acyl amino acid (NAAA), demonstrating a new biosynthetic logic for synthesizing NAAAs and expanding the chemical space of products encoded by fungal PKS-NRPS clusters.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acids / chemistry
  • Amino Acids / metabolism
  • Arabidopsis
  • Leucine / chemistry
  • Leucine / metabolism
  • Molecular Structure
  • Peptide Synthases* / genetics
  • Peptide Synthases* / metabolism
  • Plant Roots
  • Polyketide Synthases* / metabolism

Substances

  • Peptide Synthases
  • Polyketide Synthases
  • non-ribosomal peptide synthase
  • Amino Acids
  • Leucine