Advances in ε-Poly-Lysine Biosynthesis, Selection of High-Yielding Strains and Regulatory Mechanisms

ε-Poly-lysine (ε-PL) is a naturally occurring antimicrobial polypeptide that has been approved as a food preservative in several major global markets, including Japan, China, and the United States, where it is classified as Generally Recognized as Safe (GRAS). It exhibits efficacy against Gram-positive and select Gram-negative bacteria, indicating its broad potential for application in both industrial and medical sectors. The mature fermentation process of Streptomyces albulus has established it as the primary production strain for ε-PL. This article provides a comprehensive overview of the biosynthetic and antibacterial mechanisms of ε-PL and reviews the strategies for strain selection and breeding aimed at developing high-yield ε-PL-producing strains. Furthermore, it examines approaches to enhance ε-PL production through pathway-specific regulation and global metabolic engineering, while also identifying future research directions. This review aims to serve as a theoretical reference for future researchers focusing on high-yield strain breeding and metabolic engineering strategies to optimize ε-PL production. SUMMARY: The biosynthesis and antimicrobial mechanism of ε-PL are described, along with strategies for the selection of high-yielding strains. Regulatory mechanisms within the complex biosynthetic metabolism network are revealed. Strategies to improve the production of ε-PL through pathway-specific and global regulation are discussed.