Selective modification of antibiotics by biotransformation: demannosylation of ramoplanin

Ramoplanin is a glycodepsipeptide antibiotic produced by fermentation of Actinoplanes ATCC 33076 with activity against aerobic and anaerobic Gram-positive bacteria, including Staphylococcus strains resistant towards methicillin, vancomycin, ampicillin and erythromycin. Derivatives of ramoplanin show improved pharmacological activity, but its modification by synthetic methods is difficult to obtain due to its structural complexity. The use of microbial enzymes can overcome these problems by catalysing selective transformation under mild conditions. A wide screening performed among actinomycetes belonging to Vicuron collection showed that mannosyl-aglicone can be obtained by selective hydrolysis catalysed by Streptomyces GE 91081. After optimisation of the fermentation parameters, the extracellular mannosidase activity was concentrated by ultrafiltration (50000 Da) allowing for high molar conversion (> 95%) of ramoplanin into its mannosyl-aglicone derivative within 30 minutes. The biotransformation is fast and selective, while the use of commercial glycosidases resulted less selective and slow. Characterization and purification of the enzyme are under study.