Relationship between valine, fatty acids, and spiramycin biosynthesis in Streptomyces ambofaciens

Abstract

Spiramycin biosynthesis in Streptomyces ambofaciens was stimulated in the presence of valine or by sequential addition of some short-chain fatty acids to a culture medium containing an ammonium salt as source of nitrogen. Acetate kinase and acetyl-CoA carboxylase, enzymes that catalysed the formation of precursors of spiramycin biosynthesis (acetyl-CoA and malonyl-CoA), were detected during the active growth and antibiotic production phases. In this latter phase a higher level of acetyl-CoA carboxylase activity was observed with valine (1.02 mumol.min-1.mg protein-1) than with ammonium (0.05 mumol.min-1.mg protein-1) as nitrogen source, while the evolution and the level of acetate kinase activity were the same in both media. Successive addition of acetate and isobutyrate stimulated highly and weakly the acetyl-CoA carboxylase and acetate kinase activity, respectively.

Reciprocal Regulation of GlnR and PhoP in Response to Nitrogen and Phosphate Limitations in Saccharopolyspora erythraea

“…Biosynthesis of these secondary metabolites involves complex regulatory interaction networks, which are themselves finely tuned by many intra-and extracellular signals associated with physicochemical stress and the availability of carbon, nitrogen, and phosphate sources (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Concentrations of easily utilizable nitrogen and phosphate sources in the fermentation medium are critical for secondary-metabolite production (11)(12)(13)(14)(15)(16)(17).…”

Biosynthesis and Elongation of Short- and Medium-Chain-Length Fatty Acids

“…A critical re-analysis of the data used to support this pathway fails to support the hypothesis for FA elongation by onecarbon extension cycles of ␣-ketoacids. Therefore, we tested the hypothesis experimentally using criteria that distinguish between one-and two-carbon elongation mechanisms: (a) isotopomer patterns in terminal carbon atom pairs of branched and straight FAs resulting from differential labeling with The broad structural diversity of short-and mediumchain length fatty acids (scFAs and mcFAs, respectively) and their derivatives is incorporated into a wide array of biomolecules as components of antibiotics, insect pheromones, and plant storage lipids (Denoya et al, 1995;Laakel et al, 1994;Tang et al, 1994; Giblin-Davis et al, 1996;Schal et al, 1994;Pennanec' et al, 1991; Charlton and Roeloffs 1991;Knapp et al, 1991;Thompson et al, 1990; Hartman and Reimann, 1989). Understanding the biosynthesis of these compounds is critical both to understanding their regulation and designing strategies for their manipulation.…”

“…The broad structural diversity of short-and mediumchain length fatty acids (scFAs and mcFAs, respectively) and their derivatives is incorporated into a wide array of biomolecules as components of antibiotics, insect pheromones, and plant storage lipids (Denoya et al, 1995;Laakel et al, 1994;Tang et al, 1994;Giblin-Davis et al, 1996;Schal et al, 1994;Pennanec' et al, 1991;Charlton and Roeloffs 1991;Knapp et al, 1991;Thompson et al, 1990;Hartman and Reimann, 1989). Understanding the biosynthesis of these compounds is critical both to understanding their regulation and designing strategies for their manipulation.…”

Biosynthetic Origin of the Carbon Skeleton and Nitrogen Atom of Pamamycin-607, a Nitrogen-Containing Polyketide

“…7) Twelve hours after inoculation, a 15 N-labeled or nonlabeled precursor was added through filter sterilization to the production medium to a final concentration of 10 mM. NH 4 Cl or L-valine was added as an aqueous solution, and L-glutamic acid as a 0.4 N hydrochloric acid solution.…”

“…The reason for this is thought to have been dilution of the 15 N-label by non-labeled compounds in the organic nitrogen source of the medium. We thus used the spiramycin production medium 7) for the experiments with a modification; the concentration of the nitrogen source in the production medium, valine, was reduced by a half and 15 N-labeled compounds were added. The production of pamamycin, however, was one-thousandth of that in the medium used for the 13 Clabeling experiment.…”