The discovery of marine natural product Streptochlorin and its inhibition of Banana fusarium wilt by targeting the GPI pathway

Abstract

Marine actinomycetes represent a crucial reservoir of bioactive natural products, offering significant potential for developing green strategies in plant disease control. This study took Streptomyces CH06 isolated from corals in the South China Sea as the research object and systematically analyzed the antifungal mechanism of its metabolite Streptochlorin against Fusarium oxysporum f. sp. cubense Race4 (FOC4), the causative agent of banana Fusarium wilt. CH06 was identified via polyphasic taxonomy. Fermentation on Gao's No. 1 medium and LC-MS/NMR analysis yielded 10 metabolites, including novel nucleoside H7 and Streptochlorin (H5). Streptochlorin inhibited 10 phytopathogens by over 70 % at 13 μg/mL, and the EC₅₀ for FOC4 is 7 μg/mL. In the pot, Streptochlorin (20 μg/mL) achieved 95.5 % control of banana Fusarium wilt, surpassing carbendazim (89.9 %). Multi-omics analysis revealed that Streptochlorin disrupts fungal cell wall integrity by specifically inhibiting the glycosylphosphatidylinositol (GPI) targeting the GPI anchorprotein biosynthesis pathway (GPI11 protein abundance decreased to 38 % of the control). Phenotypic analyses confirmed increased membrane permeability (elevated extracellular conductivity), cell wall glucan exposure (Congo red staining), and hyphal surface blurring (TEM observations). This study for the first time elucidated the molecular mechanism by which Streptochlorin suppresses phytopathogenic fungi through targeting the GPI anchor protein biosynthesis pathway, providing novel insights for developing green fungicides derived from marine microorganisms.