Genetic dereplication driven discovery of a tricinoloniol acid biosynthetic pathway in Trichoderma hypoxylon

Genetic dereplication approach in combination with differential gene expression lead to the discovery of three new sesquiterpenes, tricinoloniol acids (TRAs) A−C (1−3) and the known fusidilactone A (4) from T. hypoxylon. Comparative transcriptomic analysis and targeted deletion identified the biosynthetic route for TRAs. Our results demonstrate an alternative application of genetic dereplication method for exploring the biosynthesis of cryptic secondary metabolites (SMs), which utilizes the coordinated expressions of trichothecene (tri) and tra cluster genes.