Dependence of turimycin biosynthesis on different substrates and its relationship to cyclic AMP levels ofStreptomyces hygroscopicus

Abstract

Cyclic AMP in general exerts a variety of effects in microorganisms that includes changes in genetic expression as well as multiple functions in regulating microbial differentiation [1,2]. The catabolite repression in Escherichia coli and other Gram-negative bacteria is the most prominent example. Evidence has been obtained which links cyclic AMP to control of a variety of metabolic processes in Streptomyces hygroscopicus including germination [3,4], growth [5,6] and phosphate inhibition of secondary metabolism [7]. The occurrence of cyclic AMP has also been described in other Streptomyces [8,9]. Both in S. hyg, roscopicus [5] and S. griseus [8] cyclic AMP levels were found to be high during growth phase and declined at the onset of stationary phase indicating that antibiotic synthesis is not regulated by catabolite repression of the E. coli-type [10,11]. However, neither the physiological parameters controlling cyclic AMP levels nor the mechanisms through which exogenous substrates influence the cellular synthesis of the cyclic nucleotide are understood. In E. coli the phosphoenolpyruvate: sugar phosphotransferase system (PTS) that catalyzes the transport of glucose and other sugars plays an important role in controlling adenylate cyclase activity [12-14]. However, strict aerobic organisms preferably use the energy of a proton-electrochemical gradient to drive transport systems directly [14,15]. S. hygroscopicus, the organism used in these experiments, produced the complex macrolide antibiotic turimycin which is structurally related to members of the leukomycin group. Turimycin is composed of a 16-membered lactone derived from acetate, propionate and butyrate [16,17], and the sugars mycaminose and mycarose. An acyl group is attached to the 4-position of the mycarose moiety. This paper describes the different effects of lower fatty acids and alcohols on turimycin production and their relationship to the levels of cyclic AMP which may be interpreted by different mechanisms of transport. Additionally, a correlation will be shown between the electrochemical potential across the plasma membrane of S. hygroscopicus with depolarizing treatment yielding cyclic AMP increases.