Catabolite repression

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Carbon catabolite repression, or simply catabolite repression, is an important part of global control system of various bacteria and other microorganisms. Catabolite repression allows microorganisms to adapt quickly to a preferred (rapidly metabolizable) carbon and energy source first. This is usually achieved through inhibition of synthesis of enzymes involved in catabolism of carbon sources other than the preferred one. The catabolite repression was first shown to be initiated by glucose and therefore sometimes referred to as the glucose effect. However, the term "glucose effect" is actually a misnomer since other carbon sources are known to induce catabolite repression.[ citation needed ]

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It was discovered by Frédéric Diénert in 1900. [1] [2] Jacques Monod provides a bibliography of pre-1940 literature. [3]

Escherichia coli

Catabolite repression was extensively studied in Escherichia coli . E. coli grows faster on glucose than on any other carbon source. For example, if E. coli is placed on an agar plate containing only glucose and lactose, the bacteria will use glucose first and lactose second. When glucose is available in the environment, the synthesis of β-galactosidase is under repression due to the effect of catabolite repression caused by glucose. The catabolite repression in this case is achieved through the utilization of phosphotransferase system.

An important enzyme from the phosphotransferase system called Enzyme II A (EIIA) plays a central role in this mechanism. There are different catabolite-specific EIIA in a single cell, even though different bacterial groups have specificities to different sets of catabolites. In enteric bacteria one of the EIIA enzymes in their set is specific for glucose transport only. When glucose levels are high inside the bacteria, EIIA mostly exists in its unphosphorylated form. This leads to inhibition of adenylyl cyclase and lactose permease, therefore cAMP levels are low and lactose can not be transported inside the bacteria.

Once the glucose is all used up, the second preferred carbon source (i.e. lactose) has to be used by bacteria. Absence of glucose will "turn off" catabolite repression. When glucose levels are low, the phosphorylated form of EIIA accumulates and consequently activates the enzyme adenylyl cyclase, which will produce high levels of cAMP. cAMP binds to catabolite activator protein (CAP) and together they will bind to a promoter sequence on the lac operon. However, this is not enough for the lactose genes to be transcribed. Lactose must be present inside the cell to remove the lactose repressor from the operator sequence (transcriptional regulation). When these two conditions are satisfied, it means for the bacteria that glucose is absent and lactose is available. Next, bacteria start to transcribe the lac operon and produce β-galactosidase enzymes for lactose metabolism. The example above is a simplification of a complex process. Catabolite repression is considered to be a part of global control system and therefore it affects more genes rather than just lactose gene transcription. [4] [5]

Bacillus subtilis

Gram positive bacteria such as Bacillus subtilis have a cAMP-independent catabolite repression mechanism controlled by catabolite control protein A (CcpA). In this alternative pathway CcpA negatively represses other sugar operons so they are off in the presence of glucose. It works by the fact that Hpr is phosphorylated by a specific mechanism, when glucose enters through the cell membrane protein EIIC, and when Hpr is phosphorylated it can then allow CcpA to block transcription of the alternative sugar pathway operons at their respective cre sequence binding sites. Note that E. coli has a similar cAMP-independent catabolite repression mechanism that utilizes a protein called catabolite repressor activator (Cra).

Related Research Articles

In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splicing to create monocistronic mRNAs that are translated separately, i.e. several strands of mRNA that each encode a single gene product. The result of this is that the genes contained in the operon are either expressed together or not at all. Several genes must be co-transcribed to define an operon.

<span class="mw-page-title-main">François Jacob</span> French biologist

François Jacob was a French biologist who, together with Jacques Monod, originated the idea that control of enzyme levels in all cells occurs through regulation of transcription. He shared the 1965 Nobel Prize in Medicine with Jacques Monod and André Lwoff.

<i>lac</i> operon Set genes encoding proteins and enzymes for lactose metabolism

The lactose operon is an operon required for the transport and metabolism of lactose in E. coli and many other enteric bacteria. Although glucose is the preferred carbon source for most enteric bacteria, the lac operon allows for the effective digestion of lactose when glucose is not available through the activity of β-galactosidase. Gene regulation of the lac operon was the first genetic regulatory mechanism to be understood clearly, so it has become a foremost example of prokaryotic gene regulation. It is often discussed in introductory molecular and cellular biology classes for this reason. This lactose metabolism system was used by François Jacob and Jacques Monod to determine how a biological cell knows which enzyme to synthesize. Their work on the lac operon won them the Nobel Prize in Physiology in 1965.

<span class="mw-page-title-main">Jacques Monod</span> French biologist

Jacques Lucien Monod was a French biochemist who won the Nobel Prize in Physiology or Medicine in 1965, sharing it with François Jacob and André Lwoff "for their discoveries concerning genetic control of enzyme and virus synthesis".

<span class="mw-page-title-main">Allolactose</span> Chemical compound

Allolactose is a disaccharide similar to lactose. It consists of the monosaccharides D-galactose and D-glucose linked through a β1-6 glycosidic linkage instead of the β1-4 linkage of lactose. It may arise from the occasional transglycosylation of lactose by β-galactosidase.

PEP group translocation, also known as the phosphotransferase system or PTS, is a distinct method used by bacteria for sugar uptake where the source of energy is from phosphoenolpyruvate (PEP). It is known to be a multicomponent system that always involves enzymes of the plasma membrane and those in the cytoplasm.

<span class="mw-page-title-main">Catabolite activator protein</span> Trans-acting transcriptional activator

Catabolite activator protein is a trans-acting transcriptional activator that exists as a homodimer in solution. Each subunit of CAP is composed of a ligand-binding domain at the N-terminus and a DNA-binding domain at the C-terminus. Two cAMP molecules bind dimeric CAP with negative cooperativity. Cyclic AMP functions as an allosteric effector by increasing CAP's affinity for DNA. CAP binds a DNA region upstream from the DNA binding site of RNA Polymerase. CAP activates transcription through protein-protein interactions with the α-subunit of RNA Polymerase. This protein-protein interaction is responsible for (i) catalyzing the formation of the RNAP-promoter closed complex; and (ii) isomerization of the RNAP-promoter complex to the open conformation. CAP's interaction with RNA polymerase causes bending of the DNA near the transcription start site, thus effectively catalyzing the transcription initiation process. CAP's name is derived from its ability to affect transcription of genes involved in many catabolic pathways. For example, when the amount of glucose transported into the cell is low, a cascade of events results in the increase of cytosolic cAMP levels. This increase in cAMP levels is sensed by CAP, which goes on to activate the transcription of many other catabolic genes.

Enzyme induction is a process in which a molecule induces the expression of an enzyme.

<span class="mw-page-title-main">Amino acid synthesis</span> The set of biochemical processes by which amino acids are produced

Amino acid biosynthesis is the set of biochemical processes by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesize all amino acids. For example, humans can synthesize 11 of the 20 standard amino acids. These 11 are called the non-essential amino acids.

The L-arabinose operon, also called the ara or araBAD operon, is an operon required for the breakdown of the five-carbon sugar L-arabinose in Escherichia coli. The L-arabinose operon contains three structural genes: araB, araA, araD, which encode for three metabolic enzymes that are required for the metabolism of L-arabinose. AraB (ribulokinase), AraA, and AraD produced by these genes catalyse conversion of L-arabinose to an intermediate of the pentose phosphate pathway, D-xylulose-5-phosphate.

Fed-batch culture is, in the broadest sense, defined as an operational technique in biotechnological processes where one or more nutrients (substrates) are fed (supplied) to the bioreactor during cultivation and in which the product(s) remain in the bioreactor until the end of the run. An alternative description of the method is that of a culture in which "a base medium supports initial cell culture and a feed medium is added to prevent nutrient depletion". It is also a type of semi-batch culture. In some cases, all the nutrients are fed into the bioreactor. The advantage of the fed-batch culture is that one can control concentration of fed-substrate in the culture liquid at arbitrarily desired levels.

The gal operon is a prokaryotic operon, which encodes enzymes necessary for galactose metabolism. Repression of gene expression for this operon works via binding of repressor molecules to two operators. These repressors dimerize, creating a loop in the DNA. The loop as well as hindrance from the external operator prevent RNA polymerase from binding to the promoter, and thus prevent transcription. Additionally, since the metabolism of galactose in the cell is involved in both anabolic and catabolic pathways, a novel regulatory system using two promoters for differential repression has been identified and characterized within the context of the gal operon.

In the field of molecular biology, the cAMP-dependent pathway, also known as the adenylyl cyclase pathway, is a G protein-coupled receptor-triggered signaling cascade used in cell communication.

<span class="mw-page-title-main">Catabolite Control Protein A</span>

Catabolite Control Protein A (CcpA) is a master regulator of carbon metabolism in gram-positive bacteria. It is a member of the LacI/GalR transcription regulator family. In contrast to most LacI/GalR proteins, CcpA is allosterically regulated principally by a protein-protein interaction, rather than a protein-small molecule interaction. CcpA interacts with the phosphorylated form of Hpr and Crh, which is formed when high concentrations of glucose or fructose-1,6-bisphosphate are present in the cell. Interaction of Hpr or Crh modulates the DNA sequence specificity of CcpA, allowing it to bind operator DNA to modulate transcription. Small molecules glucose-6-phosphate and fructose-1,6-bisphosphate are also known allosteric effectors, fine-tuning CcpA function.

Diauxic growth, diauxie or diphasic growth is any cell growth characterized by cellular growth in two phases. Diauxic growth, meaning double growth, is caused by the presence of two sugars on a culture growth media, one of which is easier for the target bacterium to metabolize. The preferred sugar is consumed first, which leads to rapid growth, followed by a lag phase. During the lag phase the cellular machinery used to metabolize the second sugar is activated and subsequently the second sugar is metabolized.

<span class="mw-page-title-main">KduI/IolB isomerase family</span> Family of enzymes

In molecular biology, the KduI/IolB isomerase family is a family of isomerase enzymes that includes 4-deoxy-L-threo-5-hexosulose-uronate ketol-isomerase (KduI) and 5-deoxy-glucuronate isomerase (IolB).

The glnALG operon is an operon that regulates the nitrogen content of a cell. It codes for the structural gene glnA the two regulatory genes glnL and glnG. glnA encodes glutamine synthetase, an enzyme which catalyzes the conversion of glutamate and ammonia to glutamine, thereby controlling the nitrogen level in the cell. glnG encodes NRI which regulates the expression of the glnALG operon at three promoters, which are glnAp1, glnAp2 located upstream of glnA) and glnLp. glnL encodes NRII which regulates the activity of NRI. No significant homology is found in Eukaryotes.

<span class="mw-page-title-main">PBAD promoter</span>

PBAD is a promoter found in bacteria and especially as part of plasmids used in laboratory studies. The promoter is a part of the arabinose operon whose name derives from the genes it regulates transcription of: araB, araA, and araD. In E. coli, the PBAD promoter is adjacent to the PC promoter, which transcribes the araC gene in the opposite direction. araC encodes the AraC protein, which regulates activity of both the PBAD and PC promoters. The cyclic AMP receptor protein CAP binds between the PBAD and PC promoters, stimulating transcription of both when bound by cAMP.

In bacterial genetics, the mal regulon is a regulon - or group of genes under common regulation - associated with the catabolism of maltose and maltodextrins. The system is especially well characterized in the model organism Escherichia coli, where it is classically described as a group of ten genes in multiple operons whose expression is regulated by a single regulatory protein, malT. MalT binds to maltose or maltodextrin and undergoes a conformational change that allows it to bind DNA at sequences near the promoters of genes required for uptake and catabolism of these sugars. The maltose regulation system in E. coli is a classic example of positive regulation. malT is regulated by catabolite repression via the catabolite activator protein. Genes under the control of malT include ATP-binding cassette transporter components, maltoporin, maltose binding protein, and several enzymes. Other Gram-negative bacteria such as Klebsiella pneumoniae have additional genes under the control of malT.

Agnes Ullmann was a French microbiologist.

References

  1. Diénert, M. Frédéric. Sur la fermentation du galactose et sur l'accoutumance des levures à ce sucre. E. Charaire, 1900. Doctoral Thesis. Published in a short form in Ann. hzst. Pasteur, 14, 139-189.
  2. Blaiseau, Pierre Louis; Holmes, Allyson M. (June 2021). "Diauxic Inhibition: Jacques Monod's Ignored Work". Journal of the History of Biology. 54 (2): 175–196. doi:10.1007/s10739-021-09639-4. ISSN   0022-5010. PMC   8376690 . PMID   33977422.
  3. Monod, Jacques (1978), "The phenomenon of enzymatic adaptation And Its Bearings on Problems of Genetics and Cellular Differentiation", Selected Papers in Molecular Biology by Jacques Monod, Elsevier, pp. 68–134, doi:10.1016/b978-0-12-460482-7.50017-8, ISBN   978-0-12-460482-7 , retrieved 2024-06-23 Alt URL
  4. Deutscher, Josef (April 2008). "The mechanisms of carbon catabolite repression in bacteria". Current Opinion in Microbiology. 11 (2): 87–93. doi:10.1016/j.mib.2008.02.007. ISSN   1369-5274. PMID   18359269.
  5. Madigan, M. T., J. M. Martinko, P. V. Dunlap, and D. P. Clark. Brock biology of microorganisms. 12th ed. San Francisco, CA: Pearson/Benjamin Cummings, 2009.