Molecular networking assisted discovery and biosynthesis elucidation of the antimicrobial spiroketals epicospirocins
Guoliang Zhu, Chengjian Hou, Weize Yuan, Zhenzhen Wang, Jingyu Zhang, Lan Jiang, Loganathan Karthik, Bixiao Li, Biao Ren, Kangjie Lv, Wanying Lu, Zhanren Cong, Huanqin Dai, Tom Hsiang, Lixin Zhang, Xueting Liu
Abstract
Two pairs of dibenzospiroketal racemates, (±)-epicospirocin A (1a/1b) and (±)-1-epi-epicospirocin A (2a/2b), and two (+)-enantiomers of aspermicrones, ent-aspermicrone B (3b) and ent-aspermicrone C (4b), together with two hemiacetal epimeric mixtures, epicospirocin B/1-epi-epicospirocin B (5/6) and epicospirocin C/1-epi-epicospirocin C (7/8), were investigated from the phytopathogenic fungus Epicoccum nigrum 09116 via MS/MS molecular networking guided isolation and chiral separation for the first time. A plausible epicospirocin biosynthetic pathway was elucidated through in silico gene function annotation together with knock-out experiments. This is the first report that has applied MS/MS molecular networking to identify intermediates correlated with a biosynthetic pathway.