Ramoplanin

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Ramoplanin is a lipoglycopeptide antibiotic.They are produced by the members of Actinoplanes.There are three factors of ramoplanin, A1,A2,A3. Ramoplanin inhibits the MurG,an essential Glycosyltransferase tat forms the glycosidic link between NAM and NAG in the biosynthesis of bacterial cell walls, and prevents the binding of UDPGlcNAc to MurG. it also interrupts the Glycotransferase activity of transglycolases.

Discovery

Ramoplanin factors A1, A2, and A3 were discovered in 1984 in the course of a Biosearch Italia (formerly Gruppo Lepetit SPA, Italy) industrial drug discovery program aimed at identifying novel antibiotics active against bacterial cell wall production from the culture broth of actinomycetes (members of the genus Actinoplanes). This discovery program relied on the development of a specific culture media that allowed the researchers to isolate in pure culture numerous Actinoplanes strains. Cell wall active antibiotics were identified from the actinomycetes culture broth based on the selective killing of methicillin-resistant Staphylococcus aureus(MRSA) over the L-form of S. aureus (a form lacking cell wall synthesis when cultured in hypotonic medium). Thus ramoplanin factors A1, A2, and A3 were isolated in 12, 72, and 16% yields, respectively, from purification of the culture broth of Actinoplanes strain ATCC 33076. Ramoplanins A1–3 differ in the length of the Nterminal acyl chain, but all have nearly identical antimicrobial activity. Soon after the discovery and isolation of factors A1–3, the media formulation was changed and the host producing strain was genetically manipulated to increase the content of factor A2 and decrease the combined content of factors A1 and A3 to �15% of the total ramoplanins.

Three additional ramoplanin factors designated A'1, A'2, and A'3 were later shown to be present in the fermentation medium, and were shown to differ from the A1, A2, and A3 components of the original complex by lacking one mannose unit from the glycosidic group. Bioconversion of A factors into A' factors was achieved by incubation with the mycelium of Actinoplanes ATCC 33076. Factor A'2 has better antibacterial activity than A2 against some bacteria.

Soon after the discovery of ramoplanins A1–3, Pfizer Central Research discovered the related antibiotic ramoplanose (3, also known as UK-71,903) from fermentation of an unnamed Actinoplanes species. Structural differences and similarities between ramoplanins A1–A3 and ramoplanose are described below. Unfortunately, no information about the biological activity of ramoplanose has been reported since its discovery.