The role of valine in the biosynthesis of penicillin N and cephalosporin C by a Cephalosporium sp.

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Abstract
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 [gamma]-hydroxyvaline. L-[14C]Valine was taken up rapidly and virtually completely by suspensions of washed mycelium but D-[14C]valine and [alpha]-oxo[14C]-isovalerate were taken up relatively slowly. 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 10-17 min. No detectable amount of L-[l4C]valine was converted into the D-isomer in the mycelium. [alpha]-Oxo[14C]isovalerate was rapidly converted into L-[ 14C]valine in mycelium and mycelial extracts. D-[l4C]Valine was partially converted into the L-isomer in the mycelium and 14C from D-valine was incorporated into protein. 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. Labelling of the antibiotics with 14C from D-[l- C]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-[l-14c]valine. Intracellular peptide material which contained, among others, residues of [alpha]-amino-adipic acid, cysteine and valine, was rapidly labelled by 14C from L_[l_14c]valine in a manner consistent with it being an intermediate in the biosynthesis of one or both of the antibiotics. Labelling of penicillin N from L-[l-14C]valine occurred more rapidly than that of cephalosporin C. However, the effects of D-valine and [gamma]-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.