Influence of short-chain fatty acids on the production of spiramycin by Streptomyces ambofaciens

Abstract

The addition of short-chain fatty acids stimulates the production of spiramycin by Streptomyces ambofaciens cultivated on dextrins and ammonium chloride. The fatty acids were activated by two enzymatic systems. The first system (acyl-CoA synthetases) was present only during the exponential phase. The second system (acylkinases coupled with acylphosphotransferases) was synthesized during the growth phase and during the stationary phase, in which spiramycin production started. Short-chain fatty acids induced the synthesis of acylkinases and acylphosphotransferases. Added at the beginning of cultures, they increased the specific activity of these enzymes during the exponential growth phase. Added at the early stationary phase, the specific activity of these enzymes and of the spiramycin production increased. Excess ammonium in the culture considerably lowered the specific activity of acylkinases synthesized in the stationary phase, when spiramycin production started. This ammonium effect can be reduced by the addition of short-chain fatty acids.

Effect of ammonium in medium on ansamitocin P-3 production by Actinosynnema pretiosum

“…In control medium, however, isobutyrate concentration was maintained at 7 mM during 48~72 h and completely consumed in the following 24 h. According to the dynamic profiles of isobutanol and isobutyrate consumption, the inhibitory effect of ammonium on AP-3 production was supposed to be partially through affecting the consumption of isobutyrate. This was in agreement with a previous report that excessive ammonium influenced the absorption of short chain fatty acids and thus antibiotic production [29]. Regarding AP-3 production, as shown in Fig.…”

Effects of glucose limitation on biomass and spiramycin production by Streptomyces ambofaciens

“…In our conditions antibiotic biosynthesis was neither inhibited nor repressed by the limiting glucose feeding during the stationary phase. The specific rate of spiramycin production was indeed close to 0.5 mg g À1 h À1 in each culture, whereas values between 0.13 and 0.5 mg g À1 h À1 are commonly reported [9,11,12]. A final spiramycin titre of 88 mg l À1 was obtained in less than 80 h without any organic acids accumulation.…”

“…This has already been observed in several streptomycetes strains and explained as a result of imbalance between glycolysis and the TCA cycle [28]. The accumulated organic acids seemed to act as an exogenous carbon reserve for later use in case of carbon limitation as previously mentioned [28] more than to act as precursors as already assumed [12]. Besides, the linear phase corresponds to a non-replicatory growth and it is commonly admitted that it results from the accumulation of intracellular reserves [22].…”

“…Three sugars, mycaminose, forosamine and mycarose, are linked to the lactone ring to form the macrolide [7]. Improvement of spiramycin production [8] and its regulation by phosphate [9,10], carbon [11][12][13] and nitrogen sources [14][15][16][17][18] has been investigated as well as genetic aspects [19][20][21].…”

Leucine improves the component of isovalerylspiramycins for the production of bitespiramycin

“…Methylbutyrate and n-butyrate, respectively derived from isoleucine and valine were the starter units of avermectin biosynthesis [10]. Meanwhile short-chain fatty acids from the catabolism of these amino acids stimulated the activity of enzymes, such as crotonyl-CoA reductase, acetyl-CoA carboxylase, acylkinase and acylphosphotransferase, which were involved in catalyzing the formation of direct precursors of macrolide antibiotics biosynthesis [11][12][13]. On the other hand, the short-chain fatty acids from the catabolism of branch-chain amino acids influenced the components of antibiotic complex [14].…”