Abstract
Epsilon-poly-l-lysine (ε-PL) is a potent antimicrobial agent, but strategies to enhance its biosynthesis remain limited due to insufficient understanding of its physiological regulation. This study explores the interaction between Streptomyces albulus and heterogeneous microbial extracts, with a focus on actinomycete-derived signals. The S. gilvosporeus extract induces the highest ε-PL production (3.4 g/L), exceeding the control by 2.6-fold and outperforming B. cinerea by 1.8-fold. Multi-omics analyses combined with morphological and biochemical profiling reveal that the induced state is characterized by intensified central carbon flux, enhanced lipid turnover, elevated respiratory activity, and cofactor regeneration, alongside suppression of competing secondary pathways. Morphological alterations, including denser mycelial aggregation and compact colony structures, accompany these metabolic shifts. Compared to B. cinerea, S. gilvosporeus elicits more pronounced stress adaptation and metabolic reprogramming in S. albulus. These findings suggest that interspecies interactions can activate intrinsic aggression resistance mechanisms, thereby driving ε-PL biosynthesis through a previously unrecognized physiological route.