Genome Mining of Epicoccum dendrobii Reveals Diverse AntimicrobialNatural 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, <b>1</b>–<b>3</b>), a new natural product (epiketide D, <b>4</b>), a diketopiperazine (boydine E, <b>5</b>), and eight known analogues <b>6</b>–<b>13</b>. Structures were elucidated via NMR, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and computational methods. Compounds <b>1</b>, <b>2</b> and <b>4</b> 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 <i>eda</i> responsible for diketopiperazines <b>5</b>–<b>10</b>. Antifungal assays revealed that wild-type E. dendrobii inhibited plant pathogen Botrytis cinerea by 56.03%, while the Δ<i>edaP</i> 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.