BIOSYNTHETIC ORIGIN OF THE CARBON SKELETON AND OXYGEN ATOMS OF THE LL-F28249α, A POTENT ANTIPARASITIC MACROLIDE

• Published in: Journal of antibiotics Vol. 42; no. 3; pp. 398 - 406
• Main Authors: TSOU, H.-R., AHMED, Z. H., FIALA, R. R., BULLOCK, M. W., CARTER, G. T., GOODMAN, J.J., BORDERS, D. B.
• Format: Journal Article
• Language: English
• Published: Tokyo JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 01.03.1989; Japan Antibiotics Research Association
• Subjects: Anti-Bacterial Agents; antibiotic LL-F28249 alpha; Antinematodal Agents - metabolism; Bacteriology; Biological and medical sciences; Fermentation; Fundamental and applied biological sciences. Psychology; Lactones - biosynthesis; Macrolides; Magnetic Resonance Spectroscopy; Metabolism. Enzymes; Microbiology; radioactive labelling; Streptomyces - metabolism; Streptomyces cyaneogriseus; Antibiotic; Oxygen; Radiolabelling; Propionic acid; Parasiticid; Biosynthesis; NMR spectrometry; Acetate; Carbon; Macrolide
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.42.398

The biosynthesis of LL-F28249α in a culture of Streptomyces cyaneogriseus has been studied using 13C, 14C and 18O labeled precursors. A complete 13C NMR spectrum of F28249α has been assigned. Incorporation studies using 13C labeled precursors indicate that the carbon skeleton of F28249α is derived from seven acetate, six propionate and one 2-methylpropionate units. The origin of the oxygen atoms of F28249α has been examined by feeding [1-13C, 18O2]acetate, [1-13C, 18O2]propionate, [2-13C]acetate/18O2 and 18O2 separately to the fermentation culture and analyzing the resulting labeled LL-F28249α samples by 13C NMR, electron impact MS and chemical ionization MS. Out of a total of eight oxygen atoms in LL-F28249α, four oxygen atoms are derived from acetate, three from propionate and one from molecular oxygen.