Journal Article

Linking a polyketide synthase gene cluster to 6-pentyl-alpha-pyrone, a Trichoderma metabolite with diverse bioactivities

Schiller, Arne, Ruzsanyi, Veronika, Pierson, Siebe, Gründlinger, Mario, Ruso, David, Büschl, Christoph, Doppler, Maria, Schuhmacher, Rainer, Schreiner, Ulrike, Stock, Valentina, Eschlböck, Alexander, Zeilinger, Susanne, Flatschacher, Daniel

2025

Overview

Background Members of the fungal genus Trichoderma are well-known for their mycoparasitic and plant protecting activities, rendering them important biocontrol agents. One of the most significant specialized metabolites (SMs) produced by various Trichoderma species is the unsaturated lactone 6-pentyl-alpha-pyrone (6-PP). Although first identified more than 50 years ago and having pronounced antifungal and plant growth-promoting properties, the biosynthetic pathway of 6-PP still remains unresolved. Results Here, we demonstrate that 6-PP is biosynthesized via the polyketide biosynthesis pathway. We identified Pks1, an iterative type I polyketide synthase, as crucial for its biosynthesis in Trichoderma atroviride , a species recognized for its prominent 6-PP production abilities. Phylogenetic and comparative genomic analyses revealed that the pks1 gene is part of a biosynthetic gene cluster conserved in those Trichoderma species that are known to produce 6-PP. Deletion of pks1 caused a complete loss of 6-PP production in T. atroviride and a significant reduction in antifungal activity against Botrytis cinerea and Rhizoctonia solani . Surprisingly, the absence of pks1 led to enhanced lateral root formation in Arabidopsis thaliana during interaction with T. atroviride . Transcriptomic analysis revealed co-regulation of pks1 with adjacent genes, including candidates coding for a C3H1-type zinc finger protein and lytic polysaccharide monooxygenase, suggesting coordination between 6-PP biosynthesis and environmental response mechanisms. Conclusion Our findings establish pks1 as an essential gene for 6-PP biosynthesis in T. atroviride , providing novel insights into the production of one of the most significant compounds of this mycoparasite. These findings may pave the way for the development of improved biocontrol agents and the application of 6-PP as potent biopesticide contributing to an eco-friendly and sustainable way of plant disease management.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: 6-pentyl-alpha-pyrone / Antifungal activity / Antifungal Agents - metabolism / Antifungal Agents - pharmacology / Applied Microbiology / Ascomycota / Biocontrol / Biological control / Biopesticides / Biosynthesis / Biosynthetic gene cluster / Biosynthetic Pathways / Biotechnology / Botrytis - drug effects / Chemical properties / Chemistry / Chemistry and Materials Science / Enzymes / Enzymology / Fungi / Fungicides / Genes / Genetic aspects / Genetic Engineering / Genomes / Genomic analysis / Hypocreales - genetics / Hypocreales - metabolism / Kinases / Light / Metabolism / Metabolites / Microbial Genetics and Genomics / Microbiological synthesis / Microbiology / Multigene Family / Pathogens / Pests / Phylogenetics / Phylogeny / PKS1 gene / Plant diseases / Plant growth / Polyketide synthase / Polyketide Synthases - genetics / Polyketide Synthases - metabolism / Polyketides / Polysaccharides / Production processes / Proteins / Pyrones - metabolism / Pyrones - pharmacology / Rhizoctonia - drug effects / Specialized metabolites / Sustainable agriculture / Transcriptomics / Trichoderma / Trichoderma - genetics / Trichoderma - metabolism / Trichoderma atroviride / Zinc finger proteins