Highly Oxygenated Caryophyllene-Type Sesquiterpenes from a Plant-Associated Fungus, <i>Pestalotiopsis hainanensis</i>, and Their Biosynthetic Gene Cluster
Yalong Zhang, Jian Bai, Daojiang Yan, Bingyu Liu, Le Zhang, Chen Zhang, Minghua Chen, Yanhua Mou, Youcai Hu
Abstract
Seven new β-caryophyllene derivatives, pestalotiphains A–G (1–7), along with six known analogues (8–13), were isolated from the plant-associated Pestalotiopsis hainanensis. Compound 1 represents the first example of a caryophyllene–adenine hybrid, and 2 contains a novel oxatricyclo[4.3.1.0] system. Their structures and absolute configurations were assigned by interpretation of a combination of spectroscopic data and electronic circular dichroism calculations. Compound 8 exhibited moderate inhibition of HL-60 and THP-1 cell lines (IC50, 6.2 and 2.0 μM, respectively). A candidate biosynthetic gene cluster responsible for these compounds was uncovered by bioinformatics analyses and confirmed by a biochemical approach.