Transcriptomic and metabolomic analyses for providing insights into the influence of polylysine synthetase on the metabolism of Streptomyces albulus

epsilon-poly-l-lysine (epsilon-PL) is the main secondary metabolite of Streptomyces albulus, and it is widely used in the food industry. Polylysine synthetase (Pls) is the last enzyme in the epsilon-PL biosynthetic pathway. Our previous study revealed that Pls overexpressed in S. albulus CICC11022 result in the efficient production of epsilon-PL. In this study, a Pls gene knockout strain was initially constructed. Then, genomic, transcriptomic and metabolomic approaches were integrated to study the effects of the high expression and knockout of Pls on the gene expression and metabolite synthesis of S. albulus. The high expression of Pls resulted in 598 significantly differentially expressed genes (DEGs) and 425 known differential metabolites, whereas the inactivation of Pls resulted in 868 significant DEGs and 374 known differential metabolites. The expressions of 8 and 35 genes were negatively and positively associated with the Pls expression, respectively. Subsequently, the influence mechanism of the high expression and inactivation of Pls on the epsilon-PL biosynthetic pathway was elucidated. Twelve metabolites with 30% decreased yield in the high-expression strain of Pls but 30% increased production in the Pls knockout strain were identified. These results demonstrate the influence of Pls on the metabolism of S. albulus. The present work can provide the theoretical basis for improving the production capacity of epsilon-PL by means of metabolic engineering or developing bioactive substances derived from S. albulus.

Automated summary

epsilon-poly-l-lysine (epsilon-PL) is a secondary metabolite produced by Streptomyces albulus and widely used in the food industry. Polylysine synthetase (Pls) is the last enzyme in the biosynthetic pathway of epsilon-PL. This study investigates the effects of Pls overexpression and knockout on gene expression and metabolite synthesis in S. albulus using genomic, transcriptomic, and metabolomic approaches. High expression of Pls leads to significant changes in gene expression and known differential metabolites, while Pls inactivation results in even more significant changes. The study also reveals the influence mechanism of Pls on the epsilon-PL biosynthetic pathway and identifies metabolites with altered production in the high-expression and knockout strains of Pls. These findings provide a theoretical basis for improving epsilon-PL production and developing bioactive substances derived from S. albulus.