Molecular Networking-Guided Discovery of New Calbistrins from Aspergillus japonicus and Integrated Omics Analyses of Their Phytotoxic Mechanism.

Abstract

Fungal species are a rich source of bioactive metabolites for agrochemical discovery. LC-MS/MS-guided molecular networking of Aspergillus japonicus led to the isolation of eight rare calbistrin-type polyketides (1-8), including three new derivatives, japonidienes J-L (1-3). Their structures were elucidated by spectroscopic analysis and computational methods. Compounds 1, 2, and 5-8 were evaluated for phytotoxicity against Eleusine indica and Amaranthus retroflexus seeds. Compounds 1 and 2 inhibited E. indica radicle elongation by 89.4% and 87.8%, respectively, comparable to glyphosate, while compounds 1, 2, and 5 inhibited A. retroflexus seedling growth more strongly than glyphosate. Integrated omics, qRT-PCR, and molecular docking/molecular dynamics simulations analyses suggested that compound 1 may affect trehalose-related metabolism through potential interaction with trehalose-6-phosphate synthase. Zebrafish embryo assays indicated relatively low developmental toxicity, supporting calbistrins as promising herbicidal leads.