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.