Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

Autor: Dongxu Zhang, Wenyu Du, Xingming Pan, Xiaoxu Lin, Fang-Ru Li, Qingling Wang, Qian Yang, Hui-Min Xu, Liao-Bin Dong
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Beilstein Journal of Organic Chemistry, Vol 20, Iss 1, Pp 815-822 (2024)
Druh dokumentu: article
ISSN: 1860-5397
DOI: 10.3762/bjoc.20.73
Popis: Drimane-type sesquiterpenoids (DMTs) are characterized by a distinctive 6/6 bicyclic skeleton comprising the A and B rings. While DMTs are commonly found in fungi and plants, their presence in bacteria has not been reported. Moreover, the biosynthetic pathways for DMTs have been primarily elucidated in fungi, with identified P450s only acting on the B ring. In this study, we isolated and characterized three bacterial DMTs, namely 3β-hydroxydrimenol (2), 2α-hydroxydrimenol (3), and 3-ketodrimenol (4), from Streptomyces clavuligerus. Through genome mining and heterologous expression, we identified a cav biosynthetic gene cluster responsible for the biosynthesis of DMTs 2–4, along with a P450, CavA, responsible for introducing the C-2 and C-3 hydroxy groups. Furthermore, the substrate scope of CavA revealed its ability to hydroxylate drimenol analogs. This discovery not only broadens the known chemical diversity of DMTs from bacteria, but also provides new insights into DMT biosynthesis in bacteria.
Databáze: Directory of Open Access Journals