Accumulation of 6-deoxyerythronolide B in a normal strain of Streptomyces erythreus and hydroxylation at carbon 6 of the erythranolide ring system by a soluble noninduced cell-free enzyme system.

Erythronolide B, a presumed intermediate in the biosynthesis of the erythromycins, has been shown to be formed from 6-deoxyerythronolide B by hydroxylation at C-6. The substrate, a metabolite of a blocked mutant of Streptomyces erythreus and postulated to be an intermediate in the biosynthesis of the erythromycins, is found also in wild-type cultures of S. erythreus CA340 either normally or in increased amount when an inhibitor of NADPH function is present. The hydroxylation of 6-deoxyerythronolide B is catalyzed by a stable and soluble cell-free enzyme preparation obtained from noninduced S. erythreus CA340, and the maximal specific activity of the hydroxylase system is found with the protein fraction precipitating between 50% and 90% of saturation with ammonium sulfate. The hydroxylase activity correlates well with the specific content of a cytochrome P-450 moiety present in the system and is inhibited by anaerobiosis and carbon monoxide.