Studies on the biosynthesis of the modified-peptide antibiotic, nosiheptide
The biosynthesis of nosiheptide, a highly modified-peptide antibiotic, was studied by feeding /sup 14/C- and /sup 13/C-labeled precursors to the producing organism, Streptomyces actuosus. To this end, methods were developed for the fermentation of S. Actuosus, and the isolation of nosiheptide. Nosiheptide was produced in a synthetic medium at levels of 175 to 200 mg/L. In addition, a HPLC method was developed for rapid and accurate assay of nosiheptide in fermentation broths. During the fermentation studies, nosiheptide production was found to be inhibited by tryptophan, cysteine, ammonia, and phosphate. Feeding experiments with DL-(3-/sup 13/C)cysteine, L-(3-/sup 13/C)serine, DL-(1-/sup 13/C)serine, L-(CH/sub 3/-/sup 13/C)methionine, and L-(2,1'-/sup 13/C/sub 2/)tryptophan uncovered the biosynthetic precursors of the residues in nosiheptide. The double-quantum NMR technique known as INADEQUATE was used to analyze nosiheptide biosynthesized from (U-/sup 13/Cnumber)glycerol. This experiment permitted unambiguous /sup 13/C-NMR assignments to be made, as well as elucidation of the biochemically maintained /sup 13/C-/sup 13/C connectivities in the conversion of the labeled glycerol to nosiheptide. Making some reasonable assumptions, a logical peptide precursor of nosiheptide is proposed: H/sub 2/N-ser-cys-thr-thr-cys-glu-cys-cys-cys-ser-cys-ser-CO/sub 2/.
- Research Organization:
- Ohio State Univ., Columbus (USA)
- OSTI ID:
- 6592244
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ALCOHOLS
AMINO ACIDS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
AROMATICS
AZAARENES
AZOLES
BACTERIA
BIOCONVERSION
BIOSYNTHESIS
CARBON 13
CARBON 14 COMPOUNDS
CARBON ISOTOPES
CARBOXYLIC ACIDS
CYSTEINE
DRUGS
EVEN-ODD NUCLEI
FERMENTATION
GLYCEROL
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROXY ACIDS
HYDROXY COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
LIPOTROPIC FACTORS
MAGNETIC RESONANCE
METHIONINE
MICROORGANISMS
NMR SPECTRA
NUCLEAR MAGNETIC RESONANCE
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PEPTIDES
PRECURSOR
PROTEINS
PYRROLES
RESONANCE
SERINE
SPECTRA
STABLE ISOTOPES
STREPTOMYCES
SYNTHESIS
THIOLS
TRACER TECHNIQUES
TRYPTOPHAN