Abstract
1. The production of penicillin N, but not that of cephalosporin C, was inhibited by the addition of d-valine to suspensions in water of washed mycelium of Cephalosporium sp. 8650. The production of cephalosporin C was selectively inhibited by γ-hydroxyvaline. 2. l-[14C]Valine was taken up rapidly and virtually completely by suspensions of washed mycelium but d-[14C]valine and α-oxo[14C]-isovalerate were taken up relatively slowly. 3. Part of the l-valine was rapidly degraded in the mycelium and part was incorporated into protein. Turnover of the valine in the amino acid pool was estimated to occur in 10–17min. 4. No detectable amount of l-[14C]valine was converted into the d-isomer in the mycelium. α-Oxo[14C]isovalerate was rapidly converted into l-[14C]valine in mycelium and mycelial extracts. 5. d-[14C]Valine was partially converted into the l-isomer in the mycelium and 14C from d-valine was incorporated into protein. 6. The labelling of penicillin N and cephalosporin C by 14C from l-[14C]valine was consistent with the view that l-valine is a direct precursor of C5 fragments of both antibiotics and that any intermediates involved are present in relatively small pools in rapid turnover. 7. Labelling of the antibiotics with 14C from d-[1-14C]valine appeared to occur after the latter had been converted into the l-isomer. Unlabelled d-valine did not decrease the efficiency of incorporation of 14C from l-[1-14C]valine. 8. Intracellular peptide material which contained, among others, residues of α-aminoadipic acid, cysteine and valine, was rapidly labelled by 14C from l-[1-14C]valine in a manner consistent with it being an intermediate in the biosynthesis of one or both of the antibiotics. 9. Labelling of penicillin N from l-[1-14C]valine occurred more rapidly than that of cephalosporin C. However, the effects of d-valine and γ-hydroxyvaline on antibiotic production and the course of labelling of the antibiotics from l-[14C]valine could not readily be explained on the assumption that penicillin N was a precursor of cephalosporin C.
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Selected References
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