Controlled biosynthesis of actinomycin with sarcosine

Abstract

Increased synthesis of actinomycins II and III occurred when sarcosine was added to the medium of growing cultures of Streptomyces antibioticus. The amount of actinomycins II and III formed depends, in part, on the concentration of sarcosine and on the time and the number of additions of this amino acid. Mycelial actinomycin, as well as that produced in the medium, contains considerable amounts of actinomycins II and III. The effect observed with sarcosine is highly specific; compounds structurally and biochemically related were ineffective. Exogenous L-proline reversed the effect of a given concentration of sarcosine; larger amounts of sarcosine abolished the activity of proline. Incorporation of DL-pipecolic acid, a proline analogue, into the medium resulted in synthesis of several new actinomycins. When washed suspensions of S. antibioticus were incubated in the presence of mM-sarcosine, there was a 5-fold increase in synthesis of actinomycin III, but no change in the percentage of actinomycin II. The results obtained support the view that exogenous sarcosine and pipecolic acid compete with and replace endogenous proline in certain actinomycin peptides. A generalized theory of actinomycin biogenesis is proposed.