Ammonium ions suppress the amino acid metabolism involved in the biosynthesis of protylonolide in a mutant of Streptomyces fradiae.

Protylonolide is a lactonic precursor of tylosin aglycone, produced by a mutant of Streptomyces fradiae. It originates from n-butyrate, propionate and acetate units. Studies were carried out using a protylonolide-producing mutant on the correlation between protylonolide biosynthesis, regulation by NH4+ and amino acid metabolism. Protylonolide production decreased in a defined medium containing high levels of NH4+, but was restored by adding lower fatty acids expected to serve as precursors of protylonolide biosynthesis. Resting cell studies demonstrated that 14C-labeled valine, threonine, leucine, isoleucine and alanine, but not lysine, were efficiently incorporated into protylonolide, indicating that these amino acids are metabolized to lower fatty acids. The incorporation of amino acids into protylonolide was reduced when the mutant strain was previously grown under high NH4+ conditions. We suggest that NH4+ suppresses the relevant amino acid metabolism, thereby reducing protylonolide formation.