Interaction between Trichoderma harzianum qt40003 and Bacillus velezensis BV25 Triggers Harzianopyridone Biosynthesis, Enhancing Biological Control Efficacy against Fusarium oxysporum f. sp. Conglutinans

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Abstract Cabbage Fusarium wilt, caused by Fusarium oxysporum f. sp. conglutinans (FOC), is a destructive soil-borne disease. Herein, we deciphered how coculture of the bacterium Bacillus velezensis BV25 with the fungus Trichoderma harzianum qt40003 activates expression of the harzianopyridone (HPY) biosynthetic gene cluster, thereby enhancing biocontrol against FOC. Greenhouse assays showed the coculture significantly enhanced biocontrol efficacy compared with single-strain treatments, reducing disease index from 88 to 26. Comparative transcriptomic analysis revealed that coculture specifically triggered transcriptional reprogramming of secondary metabolism in strain qt40003, with strong induction of the key HPY biosynthetic gene g3238. Chemical quantification confirmed that HPY yield in coculture was 5.48-fold higher than in monoculture, and purified HPY exerted potent antifungal activity against FOC with an IC50 of 28.4 μg/mL. Deletion of g3238 abolished HPY production and weakened disease control, whereas complementation restored both phenotypes. These findings demonstrate intermicrobial can activate fungal secondary metabolism to enhance biocontrol.