High-Level Poly-L-Lysine production in Streptomyces albulus by Multi-Omics-Guided Metabolic Engineering

Poly-L-lysine Is a high-valued natural food preservative mainly used to prevent food-borne pathogens and spoilage bacteria from food. Therefore, it is of great importance to construct engineered strain with efficient PL synthesis. To improve the PL production, strain with the enhanced ATP supply and PL synthetase expression were first constructed using Streptomyces albulus WG608 as cell chassis. Subsequently, integrative analysis of transcriptome and metabolome was employed to revealed the critical metabolic node related to the precursor L-lysine biosynthesis. Finally, strain WME10 with the enhanced PL synthetase expression, ATP supply and L-lysine supply was constructed, producing 64.68 g/L PL in a 5-L bioreactor, 45.94% higher than WG608. At the time of writing, our study represents the highest reported PL production in the engineered S. albulus cell factory. This work describes novel strategies to improve the PL production that potentially may be applicable for other high-value natural preservative products.