Modification of ε-poly-L-lysine in vivo to reduce self-toxicity and enhance antibiotic overproduction

epsilon-poly-L-lysine (epsilon-PL) is a novel commercial food preservative, and glucose and glycerol are two carbon sources commonly used in epsilon-PL fermentation. Using MALDI-TOF and NMR, when grown in glycerol-based medium, but not glucose-based medium is determined, Streptomyces albulus J1-005 produces a derivative of epsilon-PL in which the terminal carboxyl group is modified with the second hydroxyl group of glycerol. Interestingly, this derivative, 2-epsilon-poly(L-lys)-glycerol, was hydrolyzed back to epsilon-PL when the pH was adjusted from 3.7 to the neutral range. Antimicrobial assays indicated that, compared to epsilon-PL, 2-epsilon-poly(L-lys)-glycerol has similar inhibitory activity against several bacterial species but is less inhibitory to the producing strain. Additionally, in fed-batch fermentation, product yield was 37% higher in glycerol-based medium than in medium containing an equal amount of glucose. Hence, we propose that such culture-based approaches for modifying toxic compounds in vivo can be a promising strategy for antibiotic overproduction. (c) 2018 American Institute of Chemical Engineers