# Biosynthesis of the Fungal Cyclic Lipodepsipeptide Pleosporacin, a New Selective Inhibitor of the Phytopathogen Botrytis cinerea

## TL;DR

Researchers discovered a new compound called pleosporacin that selectively inhibits the plant pathogen Botrytis cinerea and identified its biosynthetic pathway.

## Contribution

The paper reports the discovery of pleosporacin and its biosynthetic gene cluster, enabling heterologous production in Aspergillus oryzae.

## Key findings

- Pleosporacin is a potent and selective inhibitor of Botrytis cinerea.
- The biosynthetic gene cluster for pleosporacin was identified and reconstituted in Aspergillus oryzae.
- PleB and PleC were shown to catalyze key steps in the biosynthesis of pleosporacin.

## Abstract

Bioactivity‐guided isolation led to the identification of the cyclic lipodepsipeptide pleosporacin (1) from the mycelia extract of fungal strain Pleosporales sp. IBWF 020‐21, a potent selective inhibitor of the fungal phytopathogen Botrytis cinerea. The structure and stereochemistry of 1 were elucidated by NMR and Marfey analysis, respectively. Genome mining identified a candidate biosynthetic gene cluster encoding a hexamodular nonribosomal peptide synthetases, PleA, a fatty acyl‐AMP ligase, PleB, and an aspartate decarboxylase, PleC. Reconstitution of pleABC allowed for heterologous production of 1 in Aspergillus oryzae and confirmed the identity of the ple cluster. Based on these findings a biosynthetic route is proposed, with PleB catalyzing lipoinitiation and PleC providing the nonproteinogenic amino acid β‐alanine for the assembly of 1.

Bioactivity‐guided isolation led to the discovery of a potent and selective inhibitor of the phytopathogen Botrytis cinerea, pleosporacin (1), from mycelia extracts of the fungal strain Pleosporales sp. IBWF 020‐21. The biosynthesis of the nonribosomal cyclic lipodepsipeptide 1 was elucidated via heterologous reconstitution in Aspergillus oryzae.© 2025 WILEY‐VCH GmbH