Preparation of glycolipo(depsi)peptides derivatives by biocatalysis

Focus of our research is the development of synthetically useful selective biotransformations utilizing microbial enzymes by combining natural and non-natural conditions. The presentation will deal with biotransformations as a way to generate novel glycolipo(depsi)peptide-like molecules. There are several reasons why it is important to produce derivatives of glycolipopeptide antibiotics obtained by fermentation: i.e. to better pharmacokinetics and/or pharmacodynamics, to cope with emerging resistance among gram-positive pathogens, to reduce undesirable possible side-effects. Selective hydrolysis of the fatty acid chain and/or of the sugar residues in glycolipo(depsi)peptides have been studied by chemical means, but the presence of other hydrolysable groups (i.e. the peptide bonds or the lactone in the cyclic core of these molecules) makes conventional chemistry rather complicated. Biocatalysis offers a valid alternative for performing chemo- and regio-selective hydrolysis of acyl or glycosydic bonds under mild conditions of pH, temperature and pressure. Unfortunately, commercial enzymes proved not to be useful for these modifications. Therefore, non commercial enzymes and new enzymatic activities with activity towards glycolipo(depsi)peptide have been explored using different screening approaches.. Examples from our work will be presented by including different applications: Deacylation of glycolipopeptide antibiotics (i.e dalbavancin, A40926) Deacylation of ramoplanin Demannosilation of ramoplanin These biotransformations have been accomplished on preparative scale using enzymes/whole cells from different species of actinomycetes