Dynamicomic analysis reveals the biocontrol activity of a Streptomyces avermitilis SM12 against Fusarium spp

Streptomyces avermitilis is widely recognized for its remarkable ability to produce diverse secondary metabolites with broad-spectrum antifungal activity. In this study, we employed an integrated multi-omics approach to investigate the antifungal mechanisms of S. avermitilis SM12 and explore its potential as a biocontrol agent. Genomic analysis revealed 39 biosynthetic gene clusters (BGCs), nine of which are predicted to encode antimicrobial compounds. Notably, a gene cluster showing high homology to the oligomycin biosynthetic pathway was identified. Metabolomic profiling via LC–MS and HS–SPME–GC–MS detected several antifungal metabolites, including oligomycin, phthoxazolin, ectoine, and the volatile compound 2,3-hexanedione. The cell-free supernatant obtained after 4 d fermentation significantly suppressed the growth of Fusarium solani and Fusarium oxysporum ( P  < 0.05). Subsequent in vitro assays validated the potent antifungal activity of oligomycin, ectoine, and 2,3-hexanedione. Integrated transcriptomic analysis demonstrated temporal activation of the oligomycin and phthoxazolin homologous BGC during the peak antifungal production phase, indicating its crucial role in biocontrol activity. Furthermore, time-series transcriptomics uncovered multifaceted regulatory mechanisms operating at post-transcriptional and translational levels. These results provide key insights into the coordination between BGC expression and metabolite synthesis in S. avermitilis SM12, highlighting promising targets for genetic engineering to enhance antifungal efficacy. This study systematically reveals the molecular basis of biocontrol activity in S. avermitilis SM12, supporting its potential application in sustainable agriculture.