Discovery of a Short-Chain ε-Poly-l-lysine and Its Highly Efficient Production via Synthetase Swap Strategy

• DOI: 10.1021/acs.jafc.8b06019
• Publication Date: 2019-01-14T16:55:31Z
• Authors: Delei Xu; Rui Wang; Zhaoxian Xu; Zheng Xu; Sha Li; Mingxuan Wang; Xiaohai Feng; Hong Xu
• Keywords: Ligases; 0106 biological sciences; Antifungal Agents; Bacterial Proteins; Streptomycetaceae; Yeasts; Fermentation; Polylysine; Cloning, Molecular; 01 natural sciences; Streptomyces

ε-Poly-l-lysine (ε-PL) is a natural antimicrobial cationic peptide, which is generally recognized as safe for use as a food preservative. To date, the production capacity of strains that produce low-molecular weight ε-PL remains very low and thus unsuitable for industrial production. Here, we report a new low-molecular weight ε-PL-producing Kitasatospora aureofaciens strain. The ε-PL synthase gene of this strain was cloned into a high ε-PL-producing Streptomyces albulus strain. The resulting recombinant strain efficiently produced ε-PL with a molecular weight of 1.3-2.3 kDa and yielded of 23.6 g/L following fed-batch fermentation in a 5 L bioreactor. In addition, circular dichroism spectra showed that this ε-PL takes on a conformation similar to an antiparallel pleated-sheet. Moreover, it demonstrated better antimicrobial activity against yeast compared to the 3.2-4.5 kDa ε-PL. This study provides a highly efficient strategy for production of the low-molecular weight ε-PL, which helps to expand its potential applications.