Molecular networking assisted discovery and biosynthesis elucidation of the antimicrobial spiroketals epicospirocins

• Published in: Chemical communications (Cambridge, England) Vol. 56; no. 70; p. 10171
• Main Authors: Zhu, Guoliang, Hou, Chengjian, Yuan, Weize, Wang, Zhenzhen, Zhang, Jingyu, Jiang, Lan, Karthik, Loganathan, Li, Bixiao, Ren, Biao, Lv, Kangjie, Lu, Wanying, Cong, Zhanren, Dai, Huanqin, Hsiang, Tom, Zhang, Lixin, Liu, Xueting
• Format: Journal Article
• Language: English
• Published: England 11-09-2020
• Subjects: Ascomycota - genetics; Ascomycota - metabolism; Computer Simulation; Furans - chemistry; Furans - metabolism; Spiro Compounds - chemistry; Spiro Compounds - metabolism; Stereoisomerism
• ISSN: 1364-548X
• DOI: 10.1039/d0cc03990j

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.