Differential effects of general amino acid control of lysine biosynthesis on penicillin formation in strains of Penicillium chrysogenum.

The biosynthesis of penicillin by strains Penicillium chrysogenum requires a supply of of the amino acids valine, cysteine and a-aminoadipic acid1}. a-Aminoadipic acid has received most attention since it is an intermediate of lysine biosynthesis in fungi2) and therefore forms a branch point between lysine and penicillin biosynthesis in P. chrysogenumz~6). Higher producing strains of P. chrysogenum were shown to contain higher intracellular a-aminoadipate pool concentrations during penicillin fermentation, suggesting that, although this amino acid is recycled during the last steps of penicillin biosynthesis3), the pool level is an important parameter determining the flux to penicillin6). The mechanisms in regulation of lysine biosynthesis responsible for the different steady-state levels of ct-aminoadipate are, however, not known. Jaklitsch et alP have recently shown that at the level of gene expression, lysine biosynthesis in P. chrysogenum is regulated mainly by general amino acid control8), i.e. by derepression of certain enzymes upon starvation of at least one of several amino acids, e.g. histidine or arginine. In P. chrysogenum Q 176, saccharopine reductase (EC 1.5.1.10) and saccharopine dehydrogenase (EC 1.5.1.7) are subject to general amino acid control (Fig. 1). In the higher producing strains D6/1014/A and P2 a-aminoadipate reductase is included in this regulatory process70. This difference in coarse control of the enzyme catalyzing a-aminoadipate breakdown prompted us to investigate whether changes in the activity of a-aminoadipate reductase are responsible for the increased a-aminoadipate pool size in the higher producing strains during 255