Combinatorial strain improvement and bioprocess development for efficient production of ε-poly-L-lysine in Streptomyces albulus

epsilon-Poly-L-lysine (epsilon-PL) is an amino acid homopolymer with diverse potential applications in the food, pharmaceutical and cosmetic industries. To improve its biomanufacturing efficiency, strain engineering and bioprocess optimization were combined in this study. Firstly, a cocktail strain breeding strategy was employed to generate a epsilon-PL high-production mutant, Streptomyces albulus GS114, with enhanced L-lysine uptake capability. Subsequently, the L-lysine feeding conditions during fed-batch fermentation were systematically optimized to improve the L-lysine supply, resulting in epsilon-PL production reaching 73.1 +/- 1.4 g/L in 5 L bioreactor. Finally, an engineered strain, S. albulus L2, with enhanced uptake capability and polymerization ability of L-lysine was constructed, achieving epsilon-PL production of 81.4 +/- 5.2 g/L by fed-batch fermentation. This represents the highest reported production of epsilon-PL to date. This study provided an efficient production strategy for epsilon-PL and valuable insights into the high-value utilization of L-lysine.