THE TETRACYCLIC LANTIBIOTIC ACTAGARDINE - H-1-NMR AND C-13-NMR ASSIGNMENTS AND REVISED PRIMARY STRUCTURE

The primary structure of the peptide lantibiotic actagardine was determined in (H-2(3))acetonitrile/H2O by homonuclear two- and three-dimensional NMR spectroscopy as well as 2D H-1{C-13} correlation spectra at natural abundance. Actagardine was found to be a tetracyclic 19-residue peptide containing one lanthionine and three overlapping beta-methyllanthionine bridges. Sequential resonance assignment and location of the four thioether rings was accomplished by 2D NOESY, 3D NOESY-TOCSY and gradient-enhanced H-1{C-13}-HMBC spectra. The C-terminal thioether bridge was shown to be oxidized to a sulfoxide. The NMR data were additionally confirmed by mass spectrometry and Edman degradation after chemical modification, which allowed sequencing of lanthionine and beta-methyllanthionine residues. Our studies dearly show, that the structure of actagardine as previously published by Kettenring et al. (1990) J. Antibiot. 43, 1082-1088 is not correct.