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

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.