Abstract
The bulk formation of yeast-like (arthrospore-like) cells were typical in carbon-depleted submerged cultures of the high β-lactam producer Penicillium chrysogenum NCAIM 00237 strain independently of the nitrogen-content of the culture medium. This morphogenetic switch was still quite common in carbon-starving cultures of the low-penicillin-producer strain P. chrysogenum ATCC 28089 (Wis 54-1255) when the nitrogen-content of the medium was low but was a very rare event in wild-type P. chrysogenum cultures. The mycelium→yeast-like cell transition correlated well with a relatively high glutathione concentration and a reductive glutathione/glutathione disulfite (GSH/GSSG) redox balance in autolysing cultures, which was a consequence of industrial strain development. Paradoxically, the development of high β-lactam productivity resulted in a high intracellular GSH level and, concomitantly, in an increased γ-glutamyltranspeptidase (i.e. GSH-decomposing) activity in the autolytic phase of growth of P. chrysogenum NCAIM 00237. The hypothesized causal connection between GSH metabolism and cell morphology, if verified, may help us in future metabolic engineering of industrially important filamentous fungi.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Anderson, M. E. (1985) Determination of glutathione and glutathione disulfide in biological samples. Meth. Enzymol. 113, 548–555.
Banuelos, O., Casqueiro, J., Gutierrez, S., Riano, J., Martín, J. F. (2000) The specific transport system for lysine is fully inhibited by ammonium in Penicillium chrysogenum: an ammonium-insensitive system allows uptake in carbon-starved cells. Antonie Van Leeuwenhoek 77, 91–100.
Demain, A. L., Zhang, J. (1998) Cephalosporin C production by Cephalosporium acremonium: the methionine story. Critical Rev. Biotechnol. 18, 283–294.
Emri, T., Pócsi, I., Szentirmai, A. (1997) Glutathione metabolism and protection against oxidative stress caused by peroxides in Penicillium chrysogenum. Free Radicals in Biology and Medicine 23, 809–814.
Emri, T., Leiter, É., Pócsi, I. (2000) Effect of phenoxyacetic acid on the glutathione metabolism of Penicillium chrysogenum. J. Basic Microbiol. 40, 93–104.
Emri, T., Leiter, É., Farkas, E., Pócsi, I. (2001) Penicillin productivity and glutathione-dependent detoxification of phenylacetic and phenoxyacetic acids in Penicillium chrysogenum. J. Basic Microbiol. 41, 67–73.
Emri, T., Oláh, B., Sámi, L., Pócsi, I. (2003) Does the detoxification of penicillin side-chain precursors depend on microsomal monooxygenase and glutathione S-transferase? J. Basic Microbiol. 43, 287–300.
Emri, T., Molnár, Zs., Pusztahelyi, T., Pócsi, I. (2004) Physiological and morphological changes in autolysing Aspergillus nidulans cultures. Folia Microbiol. 49, 277–284.
Emri, T., Molnár, Z., Pócsi, I. (2005) The appearances of autolytic and apoptotic markers are concomitant but differently regulated in carbon-starving Aspergillus nidulans cultures. FEMS Microbiol. Lett. 251, 297–303.
Emri, T., Molnár, Z., Pusztahelyi, T., Varecza, Z., Pocsi, I. (2005) The FluG-BrlA pathway contributes to the initialisation of autolysis in submerged Aspergillus nidulans cultures. Mycol. Res. 109, 757–763.
Emri, T., Molnár, Z., Veres, T., Pusztahelyi, T., Dudás, G., Pócsi, I. (2006) Glucose-mediated repression of autolysis and conidiogenesis in Emericella nidulans. Mycol. Res. 110, 1172–1178.
Fiddy, C., Trinci, A. P. (1976) Nuclei, septation, branching and growth of Geotrichum candidum. J. Gen. Microbiol. 97, 185–192.
Hoff, B., Schmitt, E. K., Kück, U. (2005) CPCR1, but not its interacting transcription factor AcFKH1, controls fungal arthrospore formation in Acremonium chrysogenum. Mol. Microbiol. 56, 1220–1233.
Jaspers, C. J., Gigot, D., Pennickx, M. J. (1985) Pathways of glutathione degradation in the yeast Saccharomyces cerevisiae. Phytochemistry 24, 703–707.
Johnson, B. F., Calleja, G. B., Yoo, B. Y., Zuker, M., McDonald, I. J. (1979) Cell division in yeasts. III. The biased, asymmetric location of the septum in the fission yeast cell, Schizosaccharomyces pombe. Exp. Cell Res. 123, 253–259.
Jürgensen, C. W., Jacobsen, N. R., Emri, T., Eriksen, S. H., Pócsi, I. (2001) Glutathione metabolism and dimorphism in Aureobasidium pullulans. J. Basic Microbiol. 41, 131–137.
Liu, H. (2002) Co-regulation of pathogenesis with dimorphism and phenotypic switching in Candida albicans, a commensal and a pathogen. Int. J. Med. Microbiol. 292, 299–311.
Manavathu, E., Duncan, C., Porte, Q., Gunasekaran, M. (1996) Inhibition of yeast-to mycelium conversion of Candida albicans by conjugated styryl ketones. Mycopathologia 135, 79–83.
Manavathu, M., Gunasekaran, S., Porte, Q., Manavathu, E., Gunasekaran, M. (1996) Changes in glutathione metabolic enzymes during yeast-to-mycelium conversion of Candida albicans. Canadian Journal of Microbiology 42, 76–79.
McIntyre, M., Müller, C., Dynesen, J., Nielsen, J. (2001) Metabolic engineering of the morphology of Aspergillus. Adv. Biochem. Eng./Biotechnol. 73, 103–128.
Mehdi, K., Thierie, J., Penninckx, M. J. (2001) γ-Glutamyltranspeptidase in the yeast Saccharomyces cerevisiae and its role in the vacuolar transport and metabolism of glutathione. J. Biochem. 359, 631–637.
Müller, C., McIntyre, M., Hansen, K., Nielsen, J. (2002) Metabolic engineering of the morphology of Aspergillus oryzae by altering chitin synthesis. App. Environ. Microbiol. 68, 1827–1836.
Nagy, M., Emri, T., Fekete, E., Sándor, E., Springael, J. Y., Penninckx, M. J., Pócsi, I. (2003) Glutathione metabolism of Acremonium chrysogenum in relation to cephalosporin C production: Is γ-glutamyltranspeptidase in the centre? Folia Microbiologica 48, 149–155.
Peterson, G. L. (1983) Determination of total protein. Meth. Enzymol. 91, 86–105.
Pócsi, I., Emri, T., Sámi, L., Leiter, É., Szentirmai, A. (2001) The glutathione metabolism of the β-lactam producer filamentous fungus Penicillium chrysogenum. Acta Microbiol. Immunol. Hung. 48, 393–411.
Pócsi, I., Pusztahelyi, T., Sámi, L., Emri, T. (2003) Autolysis of Penicillium chrysogenum - a holistic approach. Ind. J. Biotechnol. 2, 293–301.
Pócsi, I., Prade, R. A., Penninckx, M. J. (2004) Glutathione, altruist metabolism in fungi. Adv. Microbial Physiol. 49, 1–76.
Pócsi, I., Miskei, M., Karányi, Z., Emri, T., Ayoubi, P., Pusztahelyi, T., Balla, G., Prade, R. A. (2005) Comparison of gene expression signatures of diamide, H2O2 and menadione exposed Aspergillus nidulans cultures — linking genome-wide transcriptional changes to cellular physiology. BMC Genomics 6 (182).
Pusztahelyi, T., Pócsi, I., Kozma, J., Szentirmai, A. (1997) Aging of Penicillium chrysogenum cultures under carbon starvation: I. morphological changes and secondary metabolite production. Biotechnol. Appl. Biochem. 25, 81–86.
Pusztahelyi, T., Pócsi, I., Szentirmai, A. (1997) Aging of Penicillium chrysogenum cultures under carbon starvation: II. protease and N-acetyl-β-D-hexosaminidase production. Biotechnol. Appl. Biochemistry 25, 87–93.
Sámi, L., Emri, T., Pócsi, I. (2001) Autolysis and aging of Penicillium chrysogenum cultures under carbon starvation: III: glutathione metabolism and formation of reactive oxygen species. Mycol. Res. 105, 1246–1250.
Sámi, L., Pusztahelyi, T., Emri, T., Varecza, Z., Fekete, A., Grallert, Á., Karányi, Zs., Kiss, L., Pócsi, I. (2001) Autolysis and aging of Penicillium chrysogenum cultures under carbon starvation: chitinase production and antifungal effect of allosamidin. J. Gen. Appl. Microbiol. 47, 201–211.
San-Blas, G., San-Blas, F. (1984) Molecular aspects of fungal dimorphism. Critical Rev. Microbiol. 11, 101–127.
Schafer, F. Q., Buettner, G. R. (2001) Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radical Biology and Medicine 30, 1190–1212.
Streiblova, E. (1988) Cytological methods. In: Campbell, J., Buffers, J. M. (eds) Yeast — a Practical Approach. IRL Press, Oxford, pp. 9–49.
Sun, S. H., Sekhon, S. S., Huppert, M. (1979) Electron microscopic studies of saprobic and parasitic forms of Coccidioides immitis. Sabouraudia 17, 265–273.
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.
Thomas, D., Klein, K., Manavathu, E., Dimmock, J. R., Mutus, B. (1991) Glutathione levels during thermal induction of the yeast-to-mycelial transition in Candida albicans. FEMS Microbiol. Lett. 77, 331–334.
Todd, R. B., Greenhalgh, J. R., Hynes, M. J., Andrianopoulos, A. (2003) TupA, the Penicillium marneffei Tup1p homologue, represses both yeast and spore development. Mol. Microbiol. 48, 85–94.
Acknowledgements
The Hungarian Ministry of Education awarded a Széchenyi István Scholarship to I.P., and T.E. was a grantee of the Bolyai János Scholarship. This project was supported financially by the Office for Higher Education Programmes (grant 0092/2001) and by the OTKA (grants T034315 and T037473).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
About this article
Cite this article
Pócsi, I., Molnár, Z., Pusztahelyi, T. et al. Yeast-Like Cell Formation and Glutathione Metabolism in Autolysing Cultures of Penicillium chrysogenum. BIOLOGIA FUTURA 58, 431–440 (2007). https://doi.org/10.1556/ABiol.58.2007.4.10
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1556/ABiol.58.2007.4.10