Engineering <i>Streptomyces Albulus</i> for Efficient ε-Poly- <scp>l</scp> -lysine Production

ε-Poly-l-lysine (ε-PL), recognized for its broad antimicrobial spectrum and high water absorption, serves as a natural food preservative and superabsorbent biomaterial. However, its commercial production is limited by high production costs and low yields. To address this, a <i>Streptomyces albulus</i> mutant strain (FMME-545RX-S) was developed using combined ARTP mutagenesis and ribosomal engineering. This rifamycin- and streptomycin-resistant mutant produced 34.5 g/L ε-PL in fed-batch fermentation, a 50% increase over the parent strain (FMME-545). <i>S. albulus</i> FMME-545RX-S exhibited accelerated spore maturation, thicker hyphae, and shorter differentiation cycles. Comparative transcriptomic analysis revealed upregulated genes in amino acid, carbon, and energy metabolism. Coexpressing <i>gltA</i> and <i>nuoF</i> further increased the ε-PL titer to 40.5 g/L (17.4% higher). The optimal strain ZW2 demonstrated ε-PL production with a titer of 60.1 g/L in a 5 L fermenter after optimizing carbon source, pH, and dissolved oxygen. Overall, this study provides an efficient strategy for enhancing ε-PL production.