The emergence of resistance among Gram-positive pathogens towards glycopeptide antibiotics has stimulated the research of second-generation molecules with improved activity and expanded antimicrobial spectrum. In this paper we investigate biotransformations as a way to generate novel teicoplanin- and A40926-like molecules. A range of commercial enzymes, fungi and actinomycetes were tested on A40926 and on its semi-synthetic derivatives (MDL 63,246 and dalbavancin). Oxidation of dalbavancin to MDL 63,246 was achieved by Nonomuraea sp. ATCC 39727 and Actinomadura parvosata ATCC 53463, while Actinoplanes sp. NRRL 3884, Actinoplanes missouriensis ATCC 23342 and Actinoplanes teichomyceticus ATCC 31121 deacylated MDL 63,246, dalbavancin and A40926. It is worth noting that the actinomycetes able to catalyze the deacylation of lipoglycopeptides are themselves producers of microbiologically active glycopeptides. Structurally related antibiotics (mideplanin and teicoplanin) were not transformed. Biotransformation conditions were optimised and scaled-up for the use of Actinoplanes sp. NRRL 3884 in the production of novel deacylated derivatives.
|Titolo:||Biotransformations of lipoglycopeptides to obtain novel antibiotics|
|Parole Chiave:||Actinoplanes; Antibiotics; Biotransformation; Deacylation; Lipoglycopeptides|
|Settore Scientifico Disciplinare:||Settore CHIM/11 - Chimica e Biotecnologia delle Fermentazioni|
|Data di pubblicazione:||16-mar-2007|
|Digital Object Identifier (DOI):||10.1038/ja.2007.33|
|Appare nelle tipologie:||01 - Articolo su periodico|