# A functional atlas of secondary metabolite biosynthetic gene clusters governing growth, stress adaptation, and pathogenicity in Fusarium graminearum

## TL;DR

This study explores how secondary metabolite gene clusters in Fusarium graminearum affect growth, stress adaptation, and pathogenicity, revealing their essential roles beyond just virulence.

## Contribution

The study provides a genome-scale functional analysis of 53 SM-BGCs in Fusarium graminearum, revealing their roles in growth, stress adaptation, and pathogenicity.

## Key findings

- Secondary metabolite biosynthetic gene clusters are essential for growth, development, and stress adaptation in Fusarium graminearum.
- Two previously uncharacterized gene clusters, BGC36 and BGC47, are critical for virulence and DON production.
- SM-BGCs show spatiotemporal regulation during infection, indicating an ecological role in pathogenesis.

## Abstract

Filamentous fungi harbor a vast potential for secondary metabolite (SM) biosynthesis, yet the biological functions of numerous biosynthetic gene clusters (BGCs) remain obscure. In Fusarium graminearum, a devastating cereal pathogen, SMs are best known as virulence factors, but their broader contributions to fungal physiology are poorly defined. Here, we present a genome-scale functional dissection of 53 predicted SM-BGCs by constructing a knockout library targeting cluster backbone genes and systematically quantifying 24 phenotypic traits, generating 1,272 phenotypic measurements. This dataset reveals that secondary metabolism is not a dispensable metabolic burden; instead, SM-BGCs are broadly integrated into vegetative growth, asexual development, and abiotic stress adaptation. Transcriptome analyses further uncover pronounced spatiotemporal regulation and tissue-dependent requirements of SM-BGCs during infection of wheat heads versus coleoptiles, thereby revealing an ecological dimension of pathogenesis. Mechanistic investigation identified two previously uncharacterized clusters, PKS-type BGC36 and NRPS-type BGC47, as critical for full virulence. BGC36 positively regulates deoxynivalenol (DON) biosynthesis, whereas disruption of BGC47 compromises cell wall/membrane stress tolerance and is associated with reduced phosphorylation of the kinase Mgv1, impaired DON-toxisome formation, and reduced DON production. Together, our findings establish fungal secondary metabolism as a core physiological buffer against environmental fluctuations that supports homeostasis and virulence, and they provide a comprehensive genetic resource for dissecting the chemical biology of Fusarium.

The online version contains supplementary material available at 10.1007/s44297-026-00070-x.