Genome Mining Leads to Rare Calbistrin Derivatives with Potent Herbicidal Activity from the Endophytic Fungus Aspergillus japonicus TE-739D

Genomic mining identified a distinct cal″ biosynthetic gene cluster from the endophytic fungus Aspergillus japonicus TE-739D, thereby leading to the discovery of nine novel calbistrin derivatives, namely, japonidienes A–I (1–9), along with three known analogs (10–12). Their structures were elucidated by spectroscopic data analysis and quantum chemical calculations. Notably, compound 1 possessed a unique scaffold, in which the polyene moiety generated a cyclopentanone motif. Based on bioinformatic analyses and homology comparisons with reported calbistrin pathways, a hypothetical biosynthetic route for these isolated calbistrin-type compounds was proposed, which demonstrated an elegant example of modular polyketide assembly and diversified postmodifications. Compound 6 demonstrated potent herbicidal efficacy in suppressing Eleusine indica when compared with the positive control glyphosate. Further mechanistic investigations employing transcriptomic and proteomic analyses revealed that compound 6 disrupted MAPK signaling and influenced ABA-mediated seed dormancy pathways. This study is the first to report the herbicidal activity of rare calbistrin-type compounds, highlighting their potential as candidates for natural herbicide development.