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.