Feedback inhibition of the synthesis of an antibiotic: aurodox (X-5108)

Abstract

The effect of aurodox on its own biosynthesis by Streptomyces goldiniensis was studied. It was found that addition of exogenous aurodox inhibits further accumulation of aurodox by the antibiotic-producing culture. Both long term fermentation studies with aurodox-14C and precursor incorporation studies over short time periods indicated that aurodox synthesis was regulated by feedback inhibition. The concentration of aurodox required to completely block further synthesis of the antibiotic was about 400 microng/ml. This is the same as the maximum concentration of aurodox normally accumulated by the culture used in this study. Antibiotic synthesis was inhibited not only by aurodox but also by some structural analogs of aurodox including several having no antibacterial activity. This effect was immediate and readily reversible, indicating that it could be due to inhibition of an enzyme(s) involved in the biosynthesis of aurodox.