A21978C, A COMPLEX OF NEW ACIDIC PEPTIDE ANTIBIOTICS: ISOLATION, CHEMISTRY, AND MASS SPECTRAL STRUCTURE ELUCIDATION

• Published in: Journal of antibiotics Vol. 40; no. 6; pp. 761 - 777
• Main Authors: DEBONO, M., BARNHART, M., CARRELL, C. B., HOFFMANN, J. A., OCCOLOWITZ, J. L., ABBOTT, B. J., FUKUDA, D. S., HAMILL, R. L., BIEMANN, K., HERLIHY, W. C.
• Format: Journal Article
• Language: English
• Published: Tokyo JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 1987; Japan Antibiotics Research Association
• Subjects: Acylation; Amino Acid Sequence; Amino Acids - analysis; Anti-Bacterial Agents; Biological and medical sciences; Chemical Phenomena; Chemistry; Chromatography, High Pressure Liquid; Fatty Acids - analysis; Gas Chromatography-Mass Spectrometry; General pharmacology; Hydrolysis; Magnetic Resonance Spectroscopy; Mass Spectrometry; Medical sciences; Molecular Conformation; Peptides; Peptides, Cyclic - isolation & purification; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Spectrophotometry; Streptomyces - metabolism; Antibiotic; Purification; Peptides; Molecular structure; Bacteria; Isolation; Primary structure; Antibacterial agent
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.40.761

A21978C, produced by Streptomyces roseosporus, NRRL 11379, is a complex of new acidic lipopeptolide antibiotics which inhibits Gram-positive bacteria. HPLC separation of the various components from the purified complex resulted in the isolation of A21978C1, -C2 and -C3 (major components) and -C4, -C5 and -C0 (minor components). Each of these components was fermented with cultures of Actinoplanes utahensis (NRRL 12052) to give the identical inactive peptide ("A21978C nucleus") by removal of the fatty acid acyl groups from the TV-terminus. This peptide was composed of 13 amino acids: L-kynurenine, L-threo-3-methylglutamic acid, L-asparagine, L-aspartic acid (3 residues), glycine (2 residues), L-tryptophan, L-ornithine, D-alanine, o-serine and L-threonine. The amino acid sequence was determined using a combination of the Edman degradation and gas chromatography mass spectrum (GC-MS) analysis of appropriately derivatized peptides obtained from partial hydrolysis. Each major component was shown to be acylated with a branched chain fatty acid at the N-terminus and the structure of this fatty acid was determined by 1H NMR and mass spectral methods. A structure for A21978C was assigned on the basis of this degradative and physico-chemical information.