RESUMEN
The effect of changes in the intracellular concentration of alpha-aminoadipate on the formation of alpha-aminoadipyl-cysteinyl-valine (ACV) and isopenicillin N (IPN)--two intermediates of penicillin biosynthesis--by strains of Penicillium chrysogenum has been investigated by measuring the incorporation of radioactivity from (6-14C)-alpha-aminoadipate into cellular 14C-ACV and 14C-IPN. No ACV or IPN were found in any strain during cultivation on glucose, but were clearly detected in all three strains during growth on lactose, displaying increased formation in strains exhibiting increased penicillin productivity and increased intracellular alpha-aminoadipate pools. ACV and IPN formation was affected by subjected P. chrysogenum mycelia to either general amino acid control (by addition of amitrol) or by exogenous addition of 5 mM L-lysine. In all cases, the changes observed paralleled the changes in the intracellular alpha-aminoadipate pool. These results are consistent with the alpha-aminoadipate pool limiting the biosynthesis of ACV and IPN and hence penicillin biosynthesis in the present strains of P. chrysogenum.
Asunto(s)
Ácido 2-Aminoadípico/metabolismo , Aminoácidos Dicarboxílicos/metabolismo , Oligopéptidos/biosíntesis , Penicilinas/biosíntesis , Penicillium chrysogenum/metabolismo , Penicillium/metabolismo , Secuencia de Aminoácidos , Datos de Secuencia Molecular , Factores de TiempoRESUMEN
A partially purified preparation of alpha-aminoadipate reductase (EC 1.2.1.31) from Penicillium chrysogenum is competitively inhibited by lysine (Ki of 0.26 mM). Exogenous addition of 10 mM L-lysine to resting mycelia of P. chrysogenum increased the intracellular lysine pool concentration 2-fold, but decreased the incorporation of (6-14C)-alpha-aminoadipate into protein-bound lysine to a fifth. The distribution of radioactivity in the pathway metabolites alpha-aminoadipate, saccharopine and lysine was consistent with the assumption of a lysine sensitive enzyme step in vivo between alpha-aminoadipate and saccharopine. Hence lysine inhibition of alpha-aminoadipate reductase may be of physiologic importance.