Biotrasformation of Lipoglycopeptides

Lipoglycopeptides are an important class of antibiotics produced by actinomycetes. They still represent the drugs of last resort against multi-resistant enterococci and methicillinresistant staphylococci, but the emergence of resistance among Gram-positive pathogens towards these antibiotics has stimulated the research of second-generation molecules with improved activity and expanded antimicrobial spectrum. The lipoglycopeptide antibiotic A40926 is produced by fermentations of the actinomycete Nonomuraea sp. ATCC 39727. Besides showing an intrinsic antibacterial activity, A40926 and the structurally related teicoplanin have been used as scaffolds for the preparation of semi-synthetic derivatives such as mideplanin, MDL 63,246 and dalbavancin, the latter being in clinical development for its improved activity and better pharmacokinetics. Finally ramoplanin, a lipoglycodepsipeptide produced by Actinoplanes spp. ATCC 33076, is another potent drug active against VRE and MRSA, but its clinical use is currently limited by poor tolerability and local toxicity in animal models. In this work we investigate biotransformations as a way to generate novel glycopeptide derivatives.