Filamentous fungal secondary metabolites are an important source of bioactive components. Genome sequencing of Aspergillus terreus revealed many silent secondary metabolite biosynthetic gene clusters presumed to be involved in producing secondary metabolites. Activation of silent gene clusters through overexpressing a pathway-specific regulator is an effective avenue for discovering novel fungal secondary metabolites. Replace-ment of the native promoter of the pathway-specific activator with the inducible Tet-on system to activate the taz pathway led to the discovery of a series of azaphilone secondary metabolites, among which azaterrilone A (1) was purified and identified for the first time. Genetic deletion of core PKS genes and transcriptional analysis further characterized the taz gene cluster to consist of 16 genes with the NR-PKS and the HR-PKS collaborating in a convergent mode. Based on the putative gene functions and the characterized compounds structural infor-mation, a biosynthetic pathway of azaterrilone A (1) was proposed.
關聯:
FUNGAL GENETICS AND BIOLOGY, v.160, May 2022, 103694
