scholarly journals Yeast Carbon Catabolite Repression

1998 ◽  
Vol 62 (2) ◽  
pp. 334-361 ◽  
Author(s):  
Juana M. Gancedo

SUMMARY Glucose and related sugars repress the transcription of genes encoding enzymes required for the utilization of alternative carbon sources; some of these genes are also repressed by other sugars such as galactose, and the process is known as catabolite repression. The different sugars produce signals which modify the conformation of certain proteins that, in turn, directly or through a regulatory cascade affect the expression of the genes subject to catabolite repression. These genes are not all controlled by a single set of regulatory proteins, but there are different circuits of repression for different groups of genes. However, the protein kinase Snf1/Cat1 is shared by the various circuits and is therefore a central element in the regulatory process. Snf1 is not operative in the presence of glucose, and preliminary evidence suggests that Snf1 is in a dephosphorylated state under these conditions. However, the enzymes that phosphorylate and dephosphorylate Snf1 have not been identified, and it is not known how the presence of glucose may affect their activity. What has been established is that Snf1 remains active in mutants lacking either the proteins Grr1/Cat80 or Hxk2 or the Glc7 complex, which functions as a protein phosphatase. One of the main roles of Snf1 is to relieve repression by the Mig1 complex, but it is also required for the operation of transcription factors such as Adr1 and possibly other factors that are still unidentified. Although our knowledge of catabolite repression is still very incomplete, it is possible in certain cases to propose a partial model of the way in which the different elements involved in catabolite repression may be integrated.

2019 ◽  
Vol 85 (23) ◽  
Author(s):  
Paul Daly ◽  
Mao Peng ◽  
Marcos Di Falco ◽  
Anna Lipzen ◽  
Mei Wang ◽  
...  

ABSTRACT The extent of carbon catabolite repression (CCR) at a global level is unknown in wood-rotting fungi, which are critical to the carbon cycle and are a source of biotechnological enzymes. CCR occurs in the presence of sufficient concentrations of easily metabolizable carbon sources (e.g., glucose) and involves downregulation of the expression of genes encoding enzymes involved in the breakdown of complex carbon sources. We investigated this phenomenon in the white-rot fungus Dichomitus squalens using transcriptomics and exoproteomics. In D. squalens cultures, approximately 7% of genes were repressed in the presence of glucose compared to Avicel or xylan alone. The glucose-repressed genes included the essential components for utilization of plant biomass—carbohydrate-active enzyme (CAZyme) and carbon catabolic genes. The majority of polysaccharide-degrading CAZyme genes were repressed and included activities toward all major carbohydrate polymers present in plant cell walls, while repression of ligninolytic genes also occurred. The transcriptome-level repression of the CAZyme genes observed on the Avicel cultures was strongly supported by exoproteomics. Protease-encoding genes were generally not glucose repressed, indicating their likely dominant role in scavenging for nitrogen rather than carbon. The extent of CCR is surprising, given that D. squalens rarely experiences high free sugar concentrations in its woody environment, and it indicates that biotechnological use of D. squalens for modification of plant biomass would benefit from derepressed or constitutively CAZyme-expressing strains. IMPORTANCE White-rot fungi are critical to the carbon cycle because they can mineralize all wood components using enzymes that also have biotechnological potential. The occurrence of carbon catabolite repression (CCR) in white-rot fungi is poorly understood. Previously, CCR in wood-rotting fungi has only been demonstrated for a small number of genes. We demonstrated widespread glucose-mediated CCR of plant biomass utilization in the white-rot fungus Dichomitus squalens. This indicates that the CCR mechanism has been largely retained even though wood-rotting fungi rarely experience commonly considered CCR conditions in their woody environment. The general lack of repression of genes encoding proteases along with the reduction in secreted CAZymes during CCR suggested that the retention of CCR may be connected with the need to conserve nitrogen use during growth on nitrogen-scarce wood. The widespread repression indicates that derepressed strains could be beneficial for enzyme production.


1997 ◽  
Vol 43 (5) ◽  
pp. 432-439 ◽  
Author(s):  
Stuart M. Pitson ◽  
Robert J. Seviour ◽  
Barbara M. McDougall

The effect of carbon source on the levels of three (1 → 3)-β-glucanases and a (1 → 6)-β-glucanase in the culture filtrates of the filamentous fungus Acremonium persicinum was investigated. All four enzymes were produced during growth of the fungus on (1 → 3)-, (1 → 6)-, and (1 → 3)(1 → 6)-β-glucans as well as β-linked oligoglucosides. However, only one (1 → 3)-β-glucanase and the (1 → 6)-β-glucanase were detected during growth on a range of other carbon sources including glucose, carboxymethylcellulose, and the α-glucan pullulan. The presence of glucose in the medium markedly decreased the production of all four glucanases, although the concentration required to effect complete repression of enzyme levels varied for the different enzymes. Similar repressive effects were also observed with sucrose, fructose, and galactose. The most likely explanations for these observations are that the synthesis of the (1 → 6)-β-glucanase and one of the (1 → 3)-β-glucanases is controlled by carbon catabolite repression, while the remaining two (1 → 3)-β-glucanases are inducible enzymes subject to carbon catabolite repression.Key words: (1 → 3)-β-glucanase, (1 → 6)-β-glucanase, Acremonium persicinum, regulation of synthesis, fungal β-glucanases.


2021 ◽  
Author(s):  
Shiny Martis B ◽  
Michel Droux ◽  
William Nasser ◽  
Sylvie Reverchon ◽  
Sam Meyer

The catabolism of pectin from the plant cell walls plays a crucial role in the virulence of the phytopathogen Dickeya dadantii. In particular, the timely expression of pel genes encoding major pectate lyases is essential to circumvent the plant defense systems and induce a massive pectinolytic activity during the maceration phase. While previous studies identified the role of a positive feedback loop specific to the pectin degradation pathway, here we show that the pel> expression pattern is controlled by a metabolic switch between glucose and pectin. We develop a dynamical and quantitative regulatory model of this process integrating the two main regulators CRP and KdgR related to these two sources of carbon, and reproducing the concentration profiles of the associated metabolites, cAMP and KDG respectively, quantified using a new HPLC method. The model involves only 5 adjustable parameters, and recapitulates the dynamics of these metabolic pathways during bacterial growth together with the regulatory events occurring at the promoters of two major pel genes, pelE and pelD. It highlights their activity as an instance of carbon catabolite repression occurring at the transcriptional regulatory level, and directly related to the virulence of D. dadantii. The model also shows that quantitative differences in the binding properties of common regulators at these two promoters resulted in a qualitative different role of pelD and pelE in the metabolic switch, and also likely in conditions of infection, explaining their evolutionary conservation as separate genes in this species.


Toxins ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 697
Author(s):  
Gang Wang ◽  
Yulong Wang ◽  
Bolei Yang ◽  
Chenxi Zhang ◽  
Haiyong Zhang ◽  
...  

Carbon is one of the most important nutrients for the development and secondary metabolism in fungi. CreA is the major transcriptional factor mediating carbon catabolite repression, which is employed in the utilization of carbon sources. Aspergillus ochraceus contaminates various food and feed containing different carbon sources by producing ochratoxin A (OTA). However, little is known about the function of AoCreA in regulating the morphology and OTA production of A. ochraceus. To give an insight into the mechanism of the carbon sources regulating development of A. ochraceus and OTA production, we have identified AoCreA in A. ochraceus. The homologous recombination strategy was used to generate the AoCreA deletion mutant (ΔAoCreA). We have investigated the morphology and OTA production of the wild type (WT) and ΔAoCreA of A. ochraceus with media containing different carbon sources (glucose, fructose, maltose, D-xylose, D-mannose, acetate, D-galactose, D-mannitol and lactose). ΔAoCreA showed a significant growth and conidiation defect on all media as compared with WT. Glucose and maltose were the most inducing media for OTA production by A. ochraceus, followed by sucrose and the nutrient-rich Yeast Extract Sucrose (YES) and Potato Dextrose Agar (PDA). The deletion of AoCreA led to a drastic reduction of OTA production on all kinds of media except PDA, which was supported by the expression profile of OTA biosynthetic genes. Furthermore, infection studies of ΔAoCreA on oats and pears showed the involvement of AoCreA in the pathogenicity of A. ochraceus. Thus, these results suggest that AoCreA regulates morphological development and OTA biosynthesis in response to carbon sources in A. ochraceus.


Metabolites ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 216 ◽  
Author(s):  
Sousa ◽  
Westhoff ◽  
Methling ◽  
Lalk

Pyruvate is a key intermediate of diverse metabolic pathways of central carbon metabolism. In addition to being the end product of glycolysis, pyruvate is an essential carbon distribution point to oxidative metabolism, amino acid and fatty acid syntheses, and overflow metabolite production. Hence, a tight regulation of pyruvate kinase (Pyk) activity is of great importance. This study aimed to analyze targeted metabolites from several pathways and possible changes in Bacillus subtilis lacking Pyk. Wild type and Δpyk cells were cultivated in chemically defined medium with glucose and pyruvate as carbon sources, and the extracted metabolites were analyzed by 1H-NMR, GC-MS, HPLC-MS, and LC-MS/MS. The results showed that the perturbation created in the pyruvate node drove an adaptation to new conditions by altering the nutritional compounds’ consumption. In Δpyk, pyruvate, which is subject to glucose-dependent carbon catabolite repression, did not comply with the hierarchy in carbon source utilization. Other metabolic alterations were observed such as the higher secretion of the overflow metabolites acetoin and 2,3-butanediol by Δpyk. Our results help to elucidate the regulatory transport of glucose and pyruvate in B. subtilis and possible metabolic reroute to alternative pathways in the absence of Pyk.


2008 ◽  
Vol 190 (21) ◽  
pp. 7275-7284 ◽  
Author(s):  
Kalpana D. Singh ◽  
Matthias H. Schmalisch ◽  
Jörg Stülke ◽  
Boris Görke

ABSTRACT In many bacteria glucose is the preferred carbon source and represses the utilization of secondary substrates. In Bacillus subtilis, this carbon catabolite repression (CCR) is achieved by the global transcription regulator CcpA, whose activity is triggered by the availability of its phosphorylated cofactors, HPr(Ser46-P) and Crh(Ser46-P). Phosphorylation of these proteins is catalyzed by the metabolite-controlled kinase HPrK/P. Recent studies have focused on glucose as a repressing substrate. Here, we show that many carbohydrates cause CCR. The substrates form a hierarchy in their ability to exert repression via the CcpA-mediated CCR pathway. Of the two cofactors, HPr is sufficient for complete CCR. In contrast, Crh cannot substitute for HPr on substrates that cause a strong repression. Determination of the phosphorylation state of HPr in vivo revealed a correlation between the strength of repression and the degree of phosphorylation of HPr at Ser46. Sugars transported by the phosphotransferase system (PTS) cause the strongest repression. However, the phosphorylation state of HPr at its His15 residue and PTS transport activity have no impact on the global CCR mechanism, which is a major difference compared to the mechanism operative in Escherichia coli. Our data suggest that the hierarchy in CCR exerted by the different substrates is exclusively determined by the activity of HPrK/P.


2000 ◽  
Vol 66 (1) ◽  
pp. 277-283 ◽  
Author(s):  
Kerstin Mahr ◽  
Wolfgang Hillen ◽  
Fritz Titgemeyer

ABSTRACT The catabolite control protein CcpA is a central regulator in low-G+C-content gram-positive bacteria. It confers carbon catabolite repression to numerous genes required for carbon utilization. It also operates as a transcriptional activator of genes involved in diverse phenomena, such as glycolysis and ammonium fixation. We have cloned theccpA region of Lactobacillus pentosus. ccpAencodes a protein of 336 amino acids exhibiting similarity to CcpA proteins of other bacteria and to proteins of the LacI/GalR family of transcriptional regulators. Upstream of ccpA was found an open reading frame with similarity to the pepQ gene, encoding a prolidase. Primer extension experiments revealed two start sites of transcription for ccpA. In wild-type cells grown on glucose, mRNA synthesis occurred only from the promoter proximal toccpA. In a ccpA mutant strain, both promoters were used, with increased transcription from the distant promoter, which overlaps a presumptive CcpA binding site called cre(for catabolite responsive element). This suggests that expression ofccpA is autoregulated. Determination of the expression levels of CcpA in cells grown on repressing and nonrepressing carbon sources revealed that the amounts of CcpA produced did not change significantly, leading to the conclusion that the arrangement of two promoters may ensure constant expression of ccpA under various environmental conditions. A comparison of the genetic structures of ccpA regions revealed that lactic acid bacteria possess the gene order pepQ-ccpA-variable while the genetic structure in bacilli and Staphylococcus xylosusis aroA-ccpA-variable-acuC.


1999 ◽  
Vol 181 (9) ◽  
pp. 2863-2871 ◽  
Author(s):  
Robert A. Burne ◽  
Zezhang Thomas Wen ◽  
Yi-Ywan M. Chen ◽  
Jana E. C. Penders

ABSTRACT The polymers of fructose, levan and inulin, as well as sucrose and raffinose, are substrates for the product of the fruA gene of Streptococcus mutans GS-5. The purpose of this study was to characterize the DNA immediately flanking fruA, to explore the regulation of expression of fruA by the carbohydrate source, and to begin to elucidate the molecular basis for differential expression of the gene. Located 3′ to fruA was an open reading frame (ORF) with similarity to β-fructosidases which was cotranscribed with fruA. A transcriptional initiation site, located an appropriate distance from an extended −10-like promoter, was mapped at 165 bp 5′ to the fruA structural gene. By the use of computer algorithms, two overlapping, stable stem-loop sequences with the potential to function as rho-independent terminators were found in the 5′ untranslated region. Catabolite response elements (CREs), which have been shown to govern carbon catabolite repression (CCR) by functioning as negative ciselements in gram-positive bacteria, were located close to the promoter. The levels of production of fruA mRNA and FruA were elevated in cells growing on levan, inulin, or sucrose as the sole carbohydrate source, and repression was observed when cells were grown on readily metabolizable hexoses. Deletion derivatives containing fusions of fruA promoter regions, lacking sequences 5′ or 3′ to the promoter, and a promoterless chloramphenicol acetyltransferase gene were used (i) to demonstrate the functionality of the promoter mapped by primer extension, (ii) to demonstrate that CCR of the fru operon requires the CRE that is located 3′ to the promoter region, and (iii) to provide preliminary evidence that supports the involvement of an antitermination mechanism infruA induction.


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