A biosynthetic survey of hypocrealean biocontrol fungi
Pests cause up to 40% of global crops losses. Pesticide overuse drives resistance and poses notable risks to public health and the environment. Many hypocrealean fungi form symbiotic relationships with plants while antagonizing pests, making them valuable sources of biocontrol agents and biopesticides. However, little is known about their biosynthetic capabilities. Here we use phylogenomics, metabolomics and heterologous expression to catalog the biosynthetic repertoire of 82 plant-associated and insect-associated Hypocreales species. Annotation of 5,221 biosynthetic gene clusters reveals that ~80% of them encode unknown products. By linking biosynthetic gene clusters to molecules, we investigate the biosynthesis of several natural products, including pyridones, dethiosecoemestrin and efrapeptin. Additionally, by combining our metabologenomics workflow with synthetic biology, we characterize four nonribosomal peptide synthetase-like synthetases involved in the biosynthesis of hitherto unknown products. We believe that this work lays the groundwork for future efforts toward sustainable pest control in agriculture.
Authors
- Jay D. Keasling (ORCID: https://orcid.org/0000-0003-4170-6088)
- Dushica Arsovska
- Ana Calheiros de Carvalho (ORCID: https://orcid.org/0000-0002-7326-6913)
- Kealan Exley
- Linda Ahonen
- Sidharth Jayachandran (ORCID: https://orcid.org/0000-0003-1588-5924)
- Vijayalakshmi Kandasamy (ORCID: https://orcid.org/0000-0001-7211-8233)
- Charissa de Bekker (ORCID: https://orcid.org/0000-0002-7325-172X)
- Carolina Cano Prieto
- Daniela Rago (ORCID: https://orcid.org/0000-0002-4442-5671)
- Pablo Cruz‐Morales (ORCID: https://orcid.org/0000-0002-6751-8897)
- Agustina Undabarrena (ORCID: https://orcid.org/0000-0001-9273-0665)
- Adrian Gadar-Lopez (ORCID: https://orcid.org/0000-0002-1608-1381)
- Xiaowei Li (ORCID: https://orcid.org/0009-0008-2436-7524)
- Ling Chen (ORCID: https://orcid.org/0000-0001-6341-6191)
- Luis Caleb Damas-Ramos
- Luisa M. Trejo-Alarcon (ORCID: https://orcid.org/0000-0002-5720-523X)
- Miriam von Bargen (ORCID: https://orcid.org/0000-0003-4054-2675)
- Line Sondt-Marcussenv
- Iason Karyofyllis
- Naiara Hurtado-Lopez
- Mariana Arango Saavedra (ORCID: https://orcid.org/0000-0002-9780-0228)
- Jeppe Schack Brogaard (ORCID: https://orcid.org/0009-0004-8879-5254)
Institutions
- Lawrence Berkeley National Laboratory (US)
- Utrecht University (NL)
- Novo Nordisk Foundation (DK)
- Joint BioEnergy Institute (US)
- University of California, Berkeley (US)
- Technical University of Denmark (DK)
- Tecnológico de Monterrey (MX)
Publication Details
- Journal
- Nature Chemical Biology
- Published
- 2026-04-16
- DOI
- https://doi.org/10.1038/s41589-026-02201-5
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Novo Nordisk
- Novo Nordisk Fonden