Biosynthesis of Aminovinyl-Cysteine-Containing Peptides and Its Application in the Production of Potential Drug Candidates

Bacteria produce a wide array of metabolites to protect themselves from competing microbes. These antimicrobial compounds include peptides with an S-[(Z)-2-aminovinyl]-d-cysteine (AviCys) or S-[(Z)-2-aminovinyl]-(3S)-3-methyl-d-cysteine (AviMeCys) residue, which have been isolated from several different bacterial species. The peptides are structurally diverse: some feature polycyclic backbones, such as the lantibiotic epidermin, and others feature a mostly linear structure, such as cypemycin. Each of the AviCys-containing peptides characterized to date exhibit highly potent biological activities, ranging from antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) to anticancer activity against mouse leukemia cells. The AviCys-containing peptides gallidermin and mutacin 1140 have been suggested as possible treatments of acne and of throat infections, respectively.Unfortunately, their low production yield in fermentation (typically only 10−200 mg/L) remains a major hindrance to th...