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

ABSTRACT 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.