Genome Mining Reveals a Multiproduct Sesterterpenoid Biosynthetic Gene Cluster in Aspergillus ustus

Genome mining of Aspergillus ustus 094102 enabled the discovery of a multiproduct bifunctional terpene synthase (BTS), AuAS. Heterologous expression of AuAS led to the discovery of five new sesterterpenes, and coexpression of the upstream CYP450 monooxygenase (AuAP450) generated four new sesterterpene alcohols. Additionally, aspergilol A showed cytotoxic activities against MCF-7, MDA-MB231, and HepG2 cancer cells (IC50 21.20–48.76 μM), and aspergilol B exhibited a cytotoxic effect on MCF-7 cells (IC50 27.41 μM).