Daptomycin and Related Lipopeptides Produced by Fermentation, Chemical Modification, and Combinatorial Biosynthesis

摘要: Among the structurally related ten-membered ring acidic cyclic lipopeptide antibiotics, daptomycin was first to gain FDA approval in USA. Daptomycin and lipopeptides require Ca2+ for activity, Ca2+-bound acts as a cationic peptide interacts with negatively charged phosphotidylglycerol (PG) cytoplasmic membrane trigger its antibacterial effects. Mutants of Staphylococcus aureus, Enterococcus faecalis, faecium, Bacillus subtilis, which display incremental increases resistance daptomycin, have mutations genes that cause reductions negative charge on or thickening cell walls. approved treat skin structure infections caused by Gram-positive pathogens, bacteremia including right-sided endocarditis S. but has not been Streptococcus pneumoniae pneumonia. Many derivatives A21978C (containing core daptomycin) A54145 generated chemical modification combinatorial biosynthesis identify antibiotics superior treatment community-acquired pneumonia (CAP). Several compounds had activity were active vancomycin mouse model Lipopeptide CB-813,315, however, more than against Clostridium difficile vitro, is currently undergoing clinical trials C. difficile-associated diarrhea (CDAD).