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A resting cell system was used to study the sites of inhibition by NH4+ of protylonolide biosynthesis by a blocked mutant, strain 261, of Streptomyces fradiae. With 14C-labeled succinate or valine as an exogenous substrate, labeled protylonolide formation by high-NH4+ grown mycelia of strain 261 was lower than by low-NH4+ grown mycelia. When 14C-labeled palmitate or acetate + labeled propionate + butyrate were used as the substrates, protylonolide production by mycelia grown under the two NH4+ conditions was nearly at the same rates. It is suggested that the metabolism of succinate and valine to lower fatty acid precursors is subject to NH4+ regulation, whereas condensation of acid precursors and related steps leading to protylonolide are insensitive to NH4+ concentration.

Mechanism of nitrogen regulation of protylonolide biosynthesis in Streptomyces fradiae.