Abstract
Exploration of pathway-specific regulators is an important strategy to uncover hidden natural products. Recently, we successfully enhanced the production of novel elasnins by expressing Syo_1.56 Streptomyces antibiotic regulatory protein (SARP) in Streptomyces sp. RK18-A0406. However, initial investigations yielded a limited number of novel elasnin derivatives. To expand the chemical repertoire of metabolites produced by this engineered strain, we scaled up fermentation and implemented targeted metabolite profiling in this study, resulting in the isolation of six new elasnin C derivatives (1-6) and three new antimycins (7-9). The identified compounds exhibited antibacterial activity (IC(50) = 0.6-2.6 μg/mL) and antimalarial potential (IC(50) = 1.9-3.9 μg/mL). These findings underscore the effectiveness of regulator-based activation in unlocking the chemical diversity of microbial natural products.