Friulimicins: Novel lipopeptide antibiotics with peptidoglycan synthesis inhibiting activity from Actinoplanes friuliensis sp nov II. Isolation and structural characterization

Four novel lipopeptide antibiotics, friulimicins A, B, C, and D, were isola ted from cultures of Actinoplanes friuliensis HAG 010964 after fermentation in different nutrient media. The new compounds were separated by ion-excha nge chromatography from the acidic lipopeptides of the amphomycin type also present in the culture fluid compounds A-1437 A, B, E, and G. The principa l constituent friulimicin B, C59H94N14O19, was structurally characterized b y mass spectrometric investigations of its hydrolysis and partial degradati on products and by sequencing of the cyclic acyl peptide. The NMR data of f riulimycin B and the amphomycin constituent A-1437 B were completely assign ed by a variety of 2-D experiments, and confirmed the structures determined by mass spectrometry. All 8 lipopeptides possess an identical peptide macr ocycle as their central element, linked via diaminobutyric acid N-terminal either to an acylated asparagine residue or, in the case of the amphomycin series, to an acylated aspartic acid residue. The structures of the amphomy cins have now been revised to take account of the peptide framework describ ed herein and the determined cis-configuration of the exocyclic double bond . As a consequence of their higher isoelectric points, the new compounds fr iulimicin A, B, C, and D have different properties than the amphomycins.