Is heptelidic (koningic) acid a microbial hormone that regulates secondary metabolism in the biocontrol fungus Trichoderma virens?

Trichoderma virens, a plant- beneficial fungus, has the ability to produce volatile and non-volatile secondary metabolites that possess antimicrobial properties and contribute to promoting plant growth and development. Gliovirin, viridin, viridiol, and heptelidic acid are among its major non-volatile metabolites. In our previous study, we observed that the deletion of heptelidic acid synthase (has1), a terpene cyclase, abolished the biosynthesis of major non-volatile metabolites, in addition to heptelidic acid. Conversely, deletion of the Tex7 gene, a non-ribosomal peptide synthetase, led to an increase in heptelidic acid production, along with other major secondary metabolites. Additionally, disruption of a GAPDH gene located within a secondary metabolite gene cluster abolished heptelidic acid biosynthesis and, consequently, all major secondary metabolites. These findings suggest that heptelidic acid might act as a microbial hormone that regulates secondary metabolism. To investigate this further, we conducted transcriptomic and metabolomic comparisons between the wild-type strain and a Δhas1 mutant lacking heptelidic acid biosynthesis. Transcriptome analysis revealed a major proportion of transcripts were down regulated. Of them, nine transcripts belonged to gliovirin biosynthesis cluster, 14 for viridin cluster and five for volatile sesquiterpene and heptelidic acid biosynthesis cluster; metabolite analysis couldn't detect any heptelidic acid along with viridin, viridiol and gliovirin in the Δhas1 mutant. Additionally, several other secondary metabolites were significantly down regulated. Our results are indicative of a possibility that heptelidic acid might function as a microbial hormone regulating secondary metabolism in this biotechnologically important fungus.