Abstract
Influence of Valine, Isoleucine, and Related Compounds on Actinomycin Synthesis
Highlights
Inhibition by exogenous n-valine appears to be directly related to antibiotic synthesis, since the amount of mycelium synthesized by S. antibioticus in the presence of inhibitory concentrations of the n-isomer was found to be similar to that formed with L-valine or no valine added (Table I)
The observation that L-valine reverses the inhibitory effect of n-valine and a-methyl-nn-valine, and may even stimulate actinomycin formation, suggests that L-valine, in preference to D-V& ine, is used for synthesis of the n-valine present in an actinomycin molecule
Arnstein and Margreiter [6] have suggested that the n-configuration of amino acid residues in polypeptides and related compounds probably arises biogenetically after the formation of peptide bonds, rather than by utilization of free n-amino acids. In this connection it was shown recently that there is a greater utilization of L-cystinyl-L-(carboxy-C14) valine than L-(carboxyCl”) valine for penicillin synthesis, and that no measurable uptake of the L-cystinyl-n-(carboxy-C14) valine peptide occurred [10]
Summary
Inhibition of Actirwmycin Formation by o-Saline-The degree to which actinomycin synthesis is inhibited depends on the concentration of n-valine used and the length of incubation of the organism (Fig. 1). Nn-Valine had a striking effect upon actinomycin formation; the reduction in antibiotic titer is due solely to its n-valine content (Table I). Inhibition by exogenous n-valine appears to be directly related to antibiotic synthesis, since the amount of mycelium synthesized by S. antibioticus in the presence of inhibitory concentrations of the n-isomer was found to be similar to that formed with L-valine or no valine added (Table I). When supplied as a single addition, L-valine proved effective only in the early period of antibiotic production. This limited effect was attributed to the rapid metabolism of the L-compound in comparison with its n-isomer. If L-valine was added to the culture at intervals throughout a fermentation, a reversal of Inhibition of Actinomycin Synthesis. Inhibition of actinomycin synthesis by o-valine and a-methyl-r&valine and its reversal by L-vali-ne
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