Penicillin productivity and glutathione-dependent detoxification of phenylacetic and phenoxyacetic acids inPenicillium chrysogenum
2001; Wiley; Volume: 41; Issue: 2 Linguagem: Inglês
10.1002/1521-4028(200105)41
ISSN1521-4028
AutoresTamás Emri, Éva Leiter, Etelka Farkas, István Pócsi,
Tópico(s)Metal-Catalyzed Oxygenation Mechanisms
ResumoJournal of Basic MicrobiologyVolume 41, Issue 2 p. 67-73 Original Paper Penicillin productivity and glutathione-dependent detoxification of phenylacetic and phenoxyacetic acids in Penicillium chrysogenum Tamás Emri, Tamás Emri Department of Microbiology and Biotechnology, Faculty of Science, University of Debrecen, P.O. Box 21., H-4010 Debrecen, HungarySearch for more papers by this authorÉva Leiter, Éva Leiter Department of Microbiology and Biotechnology, Faculty of Science, University of Debrecen, P.O. Box 21., H-4010 Debrecen, HungarySearch for more papers by this authorEtelka Farkas, Etelka Farkas Department of Inorganic and Analytical Chemistry, Faculty of Science, University of Debrecen, P.O. Box 21., H-4010 Debrecen, HungarySearch for more papers by this authorIstván Pócsi Dr., István Pócsi Dr. [email protected] Department of Microbiology and Biotechnology, Faculty of Science, University of Debrecen, P.O. Box 21., H-4010 Debrecen, HungarySearch for more papers by this author Tamás Emri, Tamás Emri Department of Microbiology and Biotechnology, Faculty of Science, University of Debrecen, P.O. Box 21., H-4010 Debrecen, HungarySearch for more papers by this authorÉva Leiter, Éva Leiter Department of Microbiology and Biotechnology, Faculty of Science, University of Debrecen, P.O. Box 21., H-4010 Debrecen, HungarySearch for more papers by this authorEtelka Farkas, Etelka Farkas Department of Inorganic and Analytical Chemistry, Faculty of Science, University of Debrecen, P.O. Box 21., H-4010 Debrecen, HungarySearch for more papers by this authorIstván Pócsi Dr., István Pócsi Dr. [email protected] Department of Microbiology and Biotechnology, Faculty of Science, University of Debrecen, P.O. Box 21., H-4010 Debrecen, HungarySearch for more papers by this author First published: 05 June 2001 https://doi.org/10.1002/1521-4028(200105)41:2 3.0.CO;2-JCitations: 8AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Both toxicity and penicillin productivity of the hydroxylated derivatives of phenylacetic acid (PA) and phenoxyacetic acid (POA) were highly dependent on the position of hydroxylation on the aromatic ring in Penicillium chrysogenum. Hydroxylation at position 2 diminished penicillin production but the compounds retained most of their toxicity. On the other hand, hydroxylation at position 4 resulted in barely toxic derivatives with still significant penicillin productivity. 3-Hydroxy-PA was a weak side-chain precursor with considerably reduced toxicity. The activity of the glutathione-dependent detoxification pathway correlated well with the toxicity of the compounds but there was no correlation between acidity, toxicity and penicillin productivity. References Alonso, M.J., Bermejo, F., Reglero, A., Fernández-Cañón, J.M., González de Buitrago, G. and Luengo, J.M., 1988. Enzymatic synthesis of penicillins. J. Antibiotics, 41, 1074–1084. Anderson, M.E., 1985, Determination of glutathione and glutathione disulphide in biological samples. Methods Enzymol., 113, 548–555. Bundgaard, H. , andIlver, K.A., 1972. A new spectrophotometric method for the determination of penicillins. J. Pharm. Pharmac., 24, 790–794. Chichester, C.H., Buckpitt, A.R., Chang, A., and Plopper, C.G. 1994. Metabolism and cytotoxicity of naphthalene and its metabolites in isolated murine Clara cells. Mol. Pharmacol., 45, 664–672. Christensen, L.H., Mandrup, G., Nielsen, J. and Villadsen, J., 1994. A robust liquid chromatographic method for measurement of medium components during penicillin fermentations. Anal. Chim. Acta, 296, 51–62. Commandeur, J.N.M., Stijntjes, G.J. and Vermeulen, N.P.E., 1995. Enzymes and transport systems involved in the formation and disposition of glutathione S-conjugates. Pharmacol. Rev., 47, 271–330. Demain, A.L., and Elander, R.P., 1999. The β-lactam antibiotics: past, present, and future. Antonie van Leeuwenhoek, 75, 5–19. Emri, T., Bartók, G. and Szentirmai, A., 1994. Regulation of specific activity of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase in Penicillium chrysogenum. FEMS Microbiol. Lett., 117, 67–70. Emri, T., Leiter, É., and Pócsi, I., 2000. Effect of phenoxyacetic acid on the glutathione metabolism of Penicillium chrysogenum. J. Basic Microbiol., 40, 93–104. Eriksen, S.H., Jensen, B., Schneider, I., Kaasgaard, S., and Olsen, J., 1994. Utilization of side-chain precursors for penicillin biosynthesis in a high-producing strain of Penicillium chrysogenum. Appl. Microbiol. Biotechnol., 40, 883–887. Eriksen, S.H., Jensen, B., Schneider, I., Kaasgaard, S. and Olsen, J., 1995. Uptake of phenoxyacetic acid by Penicillium chrysogenum. Appl. Microbiol. Biotechnol., 42, 945–950. Eriksen, S.H., Søderblom, T.B.,, Jensen, B.and Olsen, J., 1998. Uptake of phenylacetic acid by two strains of Penicillium chrysogenum. Biotechnol. Bioeng., 60, 310–316. Fernández-Cañón, J.M., and Peñalva, M.A., 1995. Molecular characterization of a gene encoding a homogentisate dioxygenase from Aspergillus nidulans and identification of its human and plant homologues. J. Biol. Chem., 270, 21199–21205. Henriksen, C.M., Nielsen, J.and Villadsen, J., 1998. Modelling of the protonophoric uncoupling by phenoxyacetic acid of the plasma membrane potential of Penicillium chrysogenum. Biotechnol. Bioeng., 60, 761–767. Hillenga, D.J., Versantvoort, H.J.M., , van der Molen, S., Driessen, A.J.M., and Konings, W.N., 1995. Penicillium chrysogenum takes up the penicillin G precursor phenylacetic acid by passive diffusion. Appl. Environ. Microbiol., 61, 2589–2595. Isono, M., 1954. Oxidative metabolism of phenylacetic acid by Penicillium chrysogenum Q-176. Part 5. The production of homogentisic acid by a mutant strain induced from P. chrysogenum Q-176. (1) Isolation and identification of homogentisic acid. J. Agric. Chem. Soc. Jap., 28, 196–200. Mingot, J.M., Peñalva, M.A. and Fernández-Cañón, J.M., 1999. Disruption of phacA, an Aspergillus nidulans gene encoding a novel cytochrome P450 monooxygenase catalyzing phenylacetate 2-hydroxylation, results in penicillin overproduction. J. Biol. Chem., 274, 14545–14550. Monks, T.J., Andres, M.W., Dekant, W., Stevens, J., Lau, S.S., and van Bladern, P.J., 1990. Glutathione conjugate mediated toxicities. Toxicol. Appl. Pharmacol., 106, 1–19. Nielsen, J. and Jørgensen, H.S., 1995. Metabolic control analysis of the penicillin biosynthetic pathway in a high-yielding strain of Penicillium chrysogenum. Biotechnol. Prog., 11, 299–305. Nyiri, L., Erdélyi, A. and Lengyel, Z.L., 1966. Nonenzymatic and enzymatic hydroxylation of phenylacetic acid in Penicillium chrysogenum cultures. Z. Allg. Mikrobiol., 6, 379–386. Peterson, G.L., 1983. Determination of total protein. Methods Enzymol., 91, 86–105. Pócsi, I. and Fábián, I., 1988. Complex equilibria in aqueous solutions of Ti3+-glycine and – malonic acid. J. Chem. Soc. Dalton Trans., 2231–2233. Ramos, F.R., López-Nieto, M.J. and Martín, J.F., 1985.Isopenicillin N synthetase of Penicillium chrysogenum, an enzyme that converts δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine to isopenicillin N. Antimicrob. Agents Chemother., 27, 380–387. Sánchez, S., Flores, M.E. and Demain, A.L., 1988. Nitrogen regulation of penicillin and cephalosporin fermentations. In: Nitrogen Source Control of Microbial Processes (S. Sánchez-Esquivel, Editor), pp. 121–136. CRC Press, Boca Raton. Spallholz, J.E., 1987. Glutathione: Is it an evolutionary vestige of the penicillins? Med. Hypotheses, 23, 253–257. Spano, M., Cordelli, E., Leter, G. and Pacchierotti, F., 1998. Diepoxybutane cytotoxicity on mouse germ cells is enhanced by in vivo glutathione depletion: a flow cytometric approach. Mut. Res., 397, 37–43. Sugumaran, M., Ramanarayanan, M. and Vaidyanathan, C.S., 1973. Involvement of protocatechuic acid in the metabolism of phenylacetic acid by Aspergillus niger. FEBS Lett., 29, 69–72. Sugumaran, M. and Vaidyanathan, C.S., 1978. Metabolism of phenylacetic acid in Aspergillus niger. J. Ind. Inst. Sci., 60, 125–141. Theilgaard, H.A., Nielsen, J., 1999. Metabolic control analysis of the penicillin biosynthetic pathway: the influence of the LLD-ACV:bisACV ratio on the flux control. Antonie van Leeuwenhoek, 75, 145–154. van de Kamp, M., Driessen, A.J.M. and Konings, W.N., 1999. Compartmentalization and transport in β-lactam antibiotic biosynthesis by filamentous fungi. Antonie van Leeuwenhoek, 75, 41–78. Vlieg, J.E.T.V., Leemhuis, H., Spelberg, J.H.L. and Janssen, D.B., 2000. Characterization of the gene cluster involved in isoprene metabolism in Rhodococcus sp. strain AD45. J. Bacteriol., 182, 1956–1963. Citing Literature Volume41, Issue2May 2001Pages 67-73 ReferencesRelatedInformation
Referência(s)