Use of α-aminoadipic acid for the biosynthesis of penicillin N and cephalosporin C by a Cephalosporium sp.

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Abstract
L-[alpha]-Amino[6-14C]adipic acid has been prepared from the DL-amino actd.by oxidation of the L-isomer with L-amino acid oxidase to [alpha]-oxo[6-14C]adipic acid and by transamination of the latter with L-glutamic acid in an extract of a Cephalosporium sp. prepared by ultrasonic treatment of the mycelium. The optical configuration of small amounts of 14C-labelled [alpha]-aminoadipic acid from the mycelium of the Cephalosporium sp. has been determined by treatment with L-amino acid oxidase alid measurement of the proportion of radioactivity subsequently retained on a column of a strong cation-exchange resin. [alpha]-Aminoadipic acid which had been labelled in the mycelium from [1-14C] acetate appeared to contain more than 99 percent of the L-isomer. L- [alpha]-Aminof14C]adipic acid (sodium salt] was taken up much more rapidly than the D-isomer, or [alpha]-oxo[6-14C]adipic acid, by suspensions of washed mycelium of the Cephalosporium sp. in water. The pool of intracellular [alpha]-aminoadipic acid was expandable. Intracellular products found to be labelled with 14C from L- [alpha] -amino[14C]adipic acid were [delta] -aminovaleric acid, saccharopine, lysine, protein, compounds which behaved like penicillin N, cephalosporin C and deacetylcephalosporin C respectively on paper chromatography and electrophoresis, and a peptide whose amino acid residues include [alpha] -aminoadipic acid, cysteine and valine. L- [alpha] -Amino[14C]adipic acid acted as a precursor of the [delta]-(D-[alpha] -aminoadipoyl) side chains of extracellular penicillin N and cephalosporin C. 14C from D- [alpha] -amino[14C]adipic acid was incorporated into penicillin N and cephalosporin C, but the incorporation was accompanied by a relatively high dilution of specific radioactivity and some L- [alpha] -amino[14C]adipic acid was found in the intracellular pool. These findings are discussed in relation to the origin of the D-configuration of the [alpha]-aminoadipoyl side chain of the antibiotics.