Nutrient effects on growth and the production of 5-hydroxy-4-oxonorvaline by Streptomyces akiyoshiensis.

5-Hydroxy-4-oxonorvaline (HON) was produced optimally by Streptomyces akiyoshiensis in media containing starch and casein supplemented with high concentrations of phosphate and magnesium sulfate; cultures grown at initial pH values between 6.3 and 6.6 yielded HON titres of 13-14 mM. Physiological analysis of HON production provided evidence that the excess inorganic constituents in this medium played an important role in optimizing production. In simple defined media buffered at pH 5.5-6.0 and inoculated with either a spore suspension or washed vegetative mycelium, formation of HON was less than one-third the amount produced in the starch-casein-salts medium. Production was markedly affected by the carbon and nitrogen sources used; media containing starch and potassium nitrate or aspartate supported the highest yields of HON. In starch-nitrate media, production was suppressed by excess nitrogen source, and the HON titre decreased 3-fold as the phosphate content was increased from 0.5 to 5 mM; growth was not appreciably altered. The results suggest that the high level of HON production in the complex starch-casein-salts medium is associated with sequestration of metabolic ammonium and reduced availability of phosphate through formation of the poorly soluble magnesium ammonium phosphate.