Modification Gene Knockout Diversifies Piericidins from the Marine-Derived Streptomyces psammoticus SCSIO NS126

Piericidins are α-pyridone agricultural antibiotics produced by actinomycetes. To improve their yield and structural diversity from marine-derived Streptomyces psammoticus SCSIO NS126, this study employed homologous recombination to achieve large-fragment knockout of modification genes within the piericidin biosynthetic gene cluster. Deletion of the pie56-65 genes markedly elevated piericidin titers. Large-scale culture of the mutant afforded 21 piericidins, including 4 new analogues (1-4), and their plausible biosynthetic pathway was proposed. All isolated compounds displayed broad-spectrum antimicrobial effects, while compounds 4 and 5 showed potent activity against Staphylococcus aureus (minimum inhibitory concentration (MIC) = 0.391 μg/mL) and Alternaria solani (MIC = 0.781 μg/mL), respectively. Mechanistically, active piericidins damage pathogen membrane integrity, and compound 19 exhibited dose-dependent in vivo antifungal efficacy in plant infection assays. This study expands piericidin profiling and provides abundant candidate molecules for the development of new eco-friendly agricultural antibiotics.