Biosynthesis of the modified peptide antibiotic nosiheptide in Streptomyces actuosus
- Univ. of Washington, Seattle, WA (United States)
The biosynthesis of the highly modified thiopeptide antibiotic, nosiheptide (1), was studied by feeding radioactive and stable-isotope-labeled precursors to cultures of the producing organism, Streptomyces actuosus. The stable isotope enrichments and/or coupling patterns in the isolated 1 were analyzed by NMR spectroscopy using various 1D and 2D NMR techniques. The results complete the confirmation of the amino acid components of the antibiotic and shed light on a number of mechanistic and stereochemical aspects of its assembly from these basic building blocks. The dehydroalanine and butyrine moieties are formed by an anti elimination of water from serine and threonine, respectively, the thiazole rings from cysteine residues with loss of the pro-3R hydrogen in the oxidation step, and the hydroxypyridine moiety from two intact serine residues, situated nine amino acids apart in the peptide chain, and the carboxyl group of an adjacent cysteine. According to {sup 15}N studies which included the complete assignment of the {sup 15}N NMR resonances of 1, the carboxy-terminal amide nitrogen of 1 originates from the amino group of serine, suggesting that the precursor peptide giving rise to 1 carries an additional carboxyl-terminal serine residue which, except for its nitrogen, is removed during processing. 64 refs., 7 figs., 3 tabs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 42544
- Journal Information:
- Journal of the American Chemical Society, Vol. 115, Issue 17; Other Information: PBD: 25 Aug 1993
- Country of Publication:
- United States
- Language:
- English
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