Lysine source for ε-poly-l-lysine biosynthesis depends on diaminopimelate pathway during its production in Streptomyces albulus

Abstract

Streptomyces albulus NBRC14147 produces the polycationic homopoly(amino acid) ε-poly-l-lysine (ε-PL). Due to its antimicrobial properties, nontoxicity to humans, biodegradability, and permeability, there is a high demand for ε-PL. As ε-PL is produced by l-lysine polymerization, elucidating the source of l-lysine for ε-PL production is crucial for enhancing its yield. In actinobacteria, l-lysine is produced by diaminopimelate (DAP) pathway. In this study, 2,6-pyridine-dicarboxylate (PDC) was identified as the inhibitor of DapB, a DAP pathway enzyme, by comparing the structure of DapB from Mycobacterium tuberculosis with the model structure of DapB from S. albulus. We also found that adding PDC inhibited the growth of S. albulus. More importantly, PDC additions during the initial stages of the ε-PL production phase led to the accumulation of amino acids generated from pyruvate and l-aspartic 4-semialdehyde, while the ε-PL production was terminated. These findings suggest that de novo biosynthesized nascent l-lysine from the DAP pathway contributes to ε-PL production.