Yeast-Like Cell Formation and Glutathione Metabolism in Autolysing Cultures of Penicillium chrysogenum

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.

[1]  T. Emri,et al.  Glucose-mediated repression of autolysis and conidiogenesis in Emericella nidulans. , 2006, Mycological research.

[2]  Zsolt Karányi,et al.  Comparison of gene expression signatures of diamide, H2O2 and menadione exposed Aspergillus nidulans cultures – linking genome-wide transcriptional changes to cellular physiology , 2005, BMC Genomics.

[3]  T. Emri,et al.  The appearances of autolytic and apoptotic markers are concomitant but differently regulated in carbon-starving Aspergillus nidulans cultures. , 2005, FEMS microbiology letters.

[4]  T. Emri,et al.  The fluG-BrlA pathway contributes to the initialisation of autolysis in submerged Aspergillus nidulans cultures. , 2005, Mycological research.

[5]  U. Kück,et al.  CPCR1, but not its interacting transcription factor AcFKH1, controls fungal arthrospore formation in Acremonium chrysogenum , 2005, Molecular microbiology.

[6]  T. Emri,et al.  Does the detoxification of penicillin side‐chain precursors depend on microsomal monooxygenase and glutathione S‐transferase in Penicillium chrysogenum? , 2003, Journal of Basic Microbiology.

[7]  T. Emri,et al.  Autolysis of Penicillium chrysogenum-A Holistic Approach , 2003 .

[8]  A. Andrianopoulos,et al.  TupA, the Penicillium marneffei Tup1p homologue, represses both yeast and spore development , 2003, Molecular microbiology.

[9]  J. Nielsen,et al.  Metabolic Engineering of the Morphology of Aspergillus oryzae by Altering Chitin Synthesis , 2002, Applied and Environmental Microbiology.

[10]  M. Penninckx,et al.  gamma-Glutamyl transpeptidase in the yeast Saccharomyces cerevisiae and its role in the vacuolar transport and metabolism of glutathione. , 2001, The Biochemical journal.

[11]  T. Emri,et al.  Autolysis and ageing of Penicillium chrysogenum cultures under carbon starvation: glutathione metabolism and formation of reactive oxygen species , 2001 .

[12]  Freya Q. Schafer,et al.  Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. , 2001, Free radical biology & medicine.

[13]  N. Jacobsen,et al.  Glutathione metabolism and dimorphism in Aureobasidium pullulans , 2001, Journal of basic microbiology.

[14]  T. Emri,et al.  Penicillin productivity and glutathione‐dependent detoxification of phenylacetic and phenoxyacetic acids in Penicillium chrysogenum , 2001, Journal of basic microbiology.

[15]  T. Emri,et al.  Effect of phenoxyacetic acid on the glutathione metabolism of Penicillium chrysogenum , 2000 .

[16]  I. Pócsi,et al.  Aging of Penicillium chrysogenum cultures under carbon starvation: II: protease andN‐acetyl‐b‐D‐hexosaminidase production , 1997 .

[17]  I. Pócsi,et al.  Aging of Penicillium chrysogenum cultures under carbon starvation: I: morphological changesand secondary metabolite production , 1997 .

[18]  J. Dimmock,et al.  Glutathione levels during thermal induction of the yeast-to-mycelial transition in Candida albicans. , 1991, FEMS microbiology letters.

[19]  B. Yoo,et al.  Cell division in yeasts. III. The biased, asymmetric location of the septum in the fission yeast cell, Schizosaccharomyces pombe. , 1979, Experimental cell research.

[20]  S. Sun,et al.  Electron microscopic studies of saprobic and parasitic forms of Coccidioides immitis. , 1979, Sabouraudia.

[21]  A. Trinci,et al.  Nuclei, septation, branching and growth of Geotrichum candidum. , 1976, Journal of general microbiology.

[22]  T. Emri,et al.  Physiological and morphological changes in autolyzingAspergillus nidulans cultures , 2008, Folia Microbiologica.

[23]  J. Springael,et al.  Glutathione metabolism ofAcremonium chrysogenum in relation to cephalosporin C production: Is γ-glutamyltransferase in the center? , 2008, Folia Microbiologica.

[24]  M. Gunasekaran,et al.  Inhibition of yeast-to-mycelium conversion of Candida albicans by conjugated styryl ketones , 2004, Mycopathologia.

[25]  J. Martín,et al.  The specific transport system for lysine is fully inhibited by ammonium in Penicillium chrysogenum: An ammonium-insensitive system allows uptake in carbon-starved cells , 2004, Antonie van Leeuwenhoek.

[26]  Jens Nielsen,et al.  Metabolic control analysis of the penicillin biosynthetic pathway: the influence of the lld-ACV:bisACV ratio on the flux control , 2004, Antonie van Leeuwenhoek.

[27]  István Pócsi,et al.  Glutathione, altruistic metabolite in fungi. , 2004, Advances in microbial physiology.

[28]  Haopin Liu Co-regulation of pathogenesis with dimorphism and phenotypic switching in Candida albicans, a commensal and a pathogen. , 2002, International journal of medical microbiology : IJMM.

[29]  J. Nielsen,et al.  Metabolic engineering of the morphology of Aspergillus. , 2001, Advances in biochemical engineering/biotechnology.

[30]  T. Emri,et al.  The glutathione metabolism of the beta-lactam producer filamentous fungus Penicillium chrysogenum. , 2001, Acta microbiologica et immunologica Hungarica.

[31]  T. Emri,et al.  Autolysis and aging of Penicillium chrysogenum cultures under carbon starvation: Chitinase production and antifungal effect of allosamidin. , 2001, The Journal of general and applied microbiology.

[32]  A. Demain,et al.  Cephalosporin C production by Cephalosporium acremonium: the methionine story. , 1998, Critical reviews in biotechnology.

[33]  T. Emri,et al.  Glutathione metabolism and protection against oxidative stress caused by peroxides in Penicillium chrysogenum. , 1997, Free radical biology & medicine.

[34]  M. Gunasekaran,et al.  Changes in glutathione metabolic enzymes during yeast-to-mycelium conversion of Candida albicans. , 1996, Canadian journal of microbiology.

[35]  D. Gigot,et al.  Pathways of glutathione degradation in the yeast Saccharomyces cerevisiae , 1985 .

[36]  M. Anderson,et al.  Determination of glutathione and glutathione disulfide in biological samples. , 1985, Methods in enzymology.

[37]  F. San-Blas,et al.  Molecular aspects of fungal dimorphism. , 1984, Critical reviews in microbiology.

[38]  G. L. Peterson [12] Determination of total protein , 1983 .