Lysine biosynthesis inPenicillium chrysogenum: Regulation by general amino acid control and absence of lysine repression

doi:10.1016/0147-5975(87)90047-8

Experimental Mycology

Volume 11, Issue 2, June 1987, Pages 141-149

Experimental Mycolog...

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Abstract

Three strains ofPenicillium chrysogenum (Q176, D6/1014/A, and P2), which display different rates of penicillin biosynthesis, were examined with respect to regulation of lysine biosynthetic enzymes at the level of their biosynthesis (i.e., homocitrate synthase,α-aminoadipate aminotransferase,α-aminoadipate reductase, saccharopine reductase, and saccharopine dehydrogenase). None of these enzymes became repressed to any extent when lysine was added to the culture medium. The same behavior was seen with all three strains. General amino acid control—evoked by histidine depletion (exogenous addition of amitrole)—caused derepression of saccharopine reductase and saccharopine dehydrogenase in strain Q176, whereas the other enzymes remained unaffected. In strains D6/1014/A and P2, the same behavior was seen with the exception ofα-aminoadipate reductase, which was strongly derepressed in strain D6/1014/A and (to a lesser extent) in P2. Homocitrate synthase was not regulated by carbon catabolite repression in any of the strains.

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Metabolism and compartmentation of α-aminoadipic acid in penicillin-producing strains of Penicillium chrysogenum
1989, BBA - General Subjects
α-Aminoadipic acid is the starting amino acid for penicillin production by fungi. Using α-amino[6-¹⁴C]adipic acid, the metabolism and compartmentation of this amino acid was investigated in three strains of Penicillium chrysogenum which differed in their capacity to produce penicillin. α-Aminoadipate was shown to be the substrate of at least three concomitantly occurring metabolic routes in all three strains, i.e., lysine biosynthesis, α-aminoadipate catabolism and β-lactam synthesis. Furthermore, 6-oxopiperidine-2-car☐ylic acid — a cyclized δ-lactam of α-aminoadipate — was also found in the culture broth. During growth on glucose, no flux to β-lactam biosynthetic intermediates was observed, which coincides with carbon catabolite repression of the early enzymes of penicillin biosynthesis. During growth on lactose, flux from α-aminoadipate to lysine was strongly decreased, whereas penicillin biosynthesis occurred. The two better producing strains, D6/1014/A and P2, showed reduced catabolism and reduced flux to lysine, respectively, when compared with low producing strain Q176. This indicates that the increased α-aminoadipate pool concentration in higher producing strains (Jaklitsch et al. (1986) Can. J. Microbiol. 32, 473–480) is due to limitation in its further metabolism. By calculating specific radioactivity of the total mycelial α-aminoadipate and protein-bound lysine (which arises from α-aminoadipate), evidence was obtained for compartmentation of α-aminoadipate in a cytosolic, actively metabolized and a stable, sequestered pool. Using similar data for labeled lysine a compartmentation closely resembling other fungi was obtained. It is suggested that sequestering of α-aminoadipate may be an important factor in penicillin biosynthesis.
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The effect of changes in the intracellular concentration of α-aminoadipate on the formation of α-aminoadiphyl-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)-α-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 α-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 paralled the changes in the cellular α-aminoadipate pool. These results are consistent with the α-aminoadipate pool limiting the biosysthesis of ACV and IPN and hence penicillin biosynthesis in the present strains of P. chrysogenum.
Lysine biosynthesis in Penicillium chrysogenum is regulated by feedback inhibition of α-aminoadipate reductase
1989, FEMS Microbiology Letters
A partially purified preparation of α-aminoadipate reductase (EC 1.2.1.31) from Penicillium chrysogenum is competitively inhibited by lysine (K_i or 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)- α-aminoadipate into protein-bound lysine to a fifth. The distribution of radioactivity in the pathway metabolites α-aminoadipate, saccharopine and lysine was consistent with the assumption of a lysine sensitive enzyme step in vivo between α-aminoadipate and saccharopine. Hence lysine inhibition of α-aminoadipate reductase may be of physiologic importance.
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Regular articleLysine biosynthesis inPenicillium chrysogenum: Regulation by general amino acid control and absence of lysine repression

Abstract

Biochimie

Anal. Biochem.

Biochimie

J. Biol. Chem.

Arch. Biochem. Biophys.

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J. Biol. Chem.

Arch. Biochem. Biophys.

α-Aminoadipate pathway for the biosynthesis of lysine in lower eucaryotes

CRC Crit. Rev. Microbiol.

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Compartmental and regulatory mechanisms in the arginine pathways ofNeurospora crassa andSaccharomyces cerevisiae

Microbiol. Rev.

Regular article
Lysine biosynthesis inPenicillium chrysogenum: Regulation by general amino acid control and absence of lysine repression