Genome Mining of Epicoccum dendrobii Reveals Diverse Antimicrobial Natural Products

Epicoccum dendrobii, a biocontrol fungus, produces bioactive metabolites with potential agricultural applications. Targeted genome mining revealed 13 compounds, including three novel polyketides (epiketides A-C, 1-3), a new natural product (epiketide D, 4), a diketopiperazine (boydine E, 5), and eight known analogues 6-13. Structures were elucidated via NMR, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and computational methods. Compounds 1, 2 and 4 exhibited moderate antibacterial activity against Bacillus licheniformis (minimum inhibitory concentrations (MICs): 5.5-37.6 μM) and Pseudomonas aeruginosa (MICs: 11.1-20.0 μM). A protoplast transformation system was developed to identify the biosynthetic gene cluster eda responsible for diketopiperazines 5-10. Antifungal assays revealed that wild-type E. dendrobii inhibited plant pathogen Botrytis cinerea by 56.03%, while the ΔedaP mutant (lacking diketopiperazines) showed reduced efficacy, implying the role of diketopiperazines in antifungal activity. This study underscores E. dendrobii's potential as a biocontrol agent and provides insights into its bioactive metabolites for agricultural applications.