Effect of exogenous nucleotides on the candicidin fermentation

Area of Science:

• Microbiology
• Biochemistry
• Molecular Biology

Background:

• Streptomyces griseus produces the antibiotic candicidin.
• Factors influencing antibiotic production in microbial fermentations are of significant interest.
• The role of cyclic nucleotides in secondary metabolite production requires further elucidation.

Purpose of the Study:

• To investigate the effect of cyclic-AMP (c-AMP) on candicidin formation in Streptomyces griseus.
• To determine whether c-AMP affects precursor incorporation or protein synthesis during candicidin production.
• To compare the inhibitory effects of nucleotides with inorganic phosphate.

Main Methods:

• Streptomyces griseus fermentations were conducted with and without c-AMP addition.
• A phosphate-free resting cell system was employed.
• Incorporation of labeled propionate and p-aminobenzoic acid was measured.
• Protein synthesis levels were assessed.

Main Results:

• Addition of c-AMP significantly inhibited net candicidin formation.
• c-AMP suppressed the incorporation of labeled propionate and p-aminobenzoic acid into candicidin.
• Protein synthesis remained unaffected by c-AMP treatment.
• All tested nucleotides, irrespective of phosphate ester position, acted as inhibitors, while nucleosides and free bases did not.

Conclusions:

• Exogenous nucleotides, including cyclic nucleotides like c-AMP, inhibit candicidin formation in Streptomyces griseus.
• The mechanism of inhibition by nucleotides appears analogous to that of inorganic phosphate.
• Antibiotic biosynthesis is selectively targeted by these nucleotide-mediated inhibitions, distinct from general protein synthesis.