Lac operon is an abbreviated form of lactose operon. Lactose operon is used for transporting and metabolising the lactose in E. coli and many other enteric bacteria.
Though glucose is considered a preferred carbon source for most bacteria, the activity of operon allows for the digestion of lactose effectively when the glucose is not available through the activity of the beta-galactosidase.
Gene regulation of the lac operon is considered as the first genetic regulatory mechanism which helps us to understand the concept clearly.
So, it became a common example of prokaryotic gene regulation. Before knowing about the lac operon, it is very much important to know about gene regulation.
Features of Lac Operon
Lac operon is generally defined as the group of genes which has a single promoter that encodes the genes for the transport and the metabolism of the lactose in the bacterium Escherichia coli and other species of bacteria.
Gene regulation in the prokaryotes can be explained with the help of the model of the lac operon.
The alteration in the physiological and environmental conditions are observed leading to an alteration in the expression of genes in a prokaryote.
This concept was first observed by Jacob and Monod.
The lac operon consists of the following;
Regulatory gene: It is usually represented by the letter I, It codes for the repressor proteins.
z gene: Its codes for the enzyme beta-galactosidase which catalyzes the hydrolysis of the lactose into glucose and galactose.
Y gene: This gene codes for the enzyme permease which helps in regulating the lactose permeability in the cell.
a gene: It usually codes for transacetylase and assists in the formation of the enzyme beta-galactosidase.
All these genes help in lactose metabolism. However, In the lac operon, lactose acts as an inducer.
The regulatory gene is activated when the lactose is provided with a medium of bacteria. Then the lactose which is acting as an inducer binds with the repressor proteins and renders the protein to get inactivated and allows the transcription of the operon. So, the lac operon is negatively regulated in such cases.
Bacterial Lac Operon
Bacterial operons are polycistronic transcripts, that can produce multiple proteins from a single mRNA transcript. When lactose is required as a sugar source for the bacterium, three genes of the lac operon are expressed, and also their subsequent proteins are translated: lacZ, lacy, and lac A.
Whereas the gene product of lac Z is known as beta-galactosidase which plays an active role in cleaving lactose into a monosaccharide as glucose and galactose.
Lac Y encodes for the enzyme Beta-galactosidase permease which is a membrane protein and it becomes embedded in a cytoplasmic membrane and thus enables the cellular transport of the lactose into the cell and lac A encodes for Galactosidase acetyltransferase; this is used to produce the enzymes when there is no availability of the lactose, it has also been used when enough glucose is not available to get a required amount of energy.
Lac operon generally uses two parts as the control mechanism for ensuring the energy expenditure by the cells for the production of enzymes that are encoded by the lac operon only when they are necessary.
At the time of absence of lactose, lac repressor (lacI) depresses or halts the production of enzymes that are encoded by lac operon.
Lac repressor is always in an expressed form unless a co-inducer binds to it. It can also be said that lac operon transcribes only in the presence of a small molecule co-inducer.
In the presence of glucose, catabolite activator protein is required for the production of enzymes, which shutdowns lactose permease for preventing the transport of lactose in a cell.
This dual mechanism causes the sequential utilization of glucose and lactose into two distinct phases of growth, which is known as diauxie.
Structure of Lac Operon
Lac operon contains about 3 structural genes along with a promoter, regulator, terminator, and operator. The structural genes are named lacz, lacY, and lacA.
Lac Z encodes for Beta-galactosidase, which is an intracellular enzyme and cleaves the disaccharide lactose into glucose and galactose.
Lac Y encodes for Beta-galactoside permease, which is a transmembrane symporter that pumps the Beta-galactosides including lactose into the cell using a gradient of protein in the same direction.
Permease increases the permeability of the cell. Lac A encodes for Beta-galactosidase transacetylase which transfers an acetyl group, acetyl-CoA to thiogalactoside.
In this only lacZ and lac, Y is needed for the catabolism of the lactose.
Regulation of Lac Operon
The activity which controls the expression of the lac operon is regulated by two different kinds of proteins. Where one of the proteins prevents the RNA polymerase from transcribing and is known as the negative control, and the other protein enhances the building of the enzyme RNA polymerase and is known as the positive control.
Negative Regulation of Lac Operon
The proteins which inhibit the process of transcription in lac operon is a tetramer with four identical subunits and they are generally known as lac repressor.
This lac repressor is encoded by a lacI gene, which is located upstream of the lac operon and also consists of its promoter.
Expression of lacI gene is not regulated and only very low levels of the lac repressor are synthesized continuously.
Genes whose expression cannot be regulated are said to be constitutive genes. At the time of absence of the lactose, the lac repressor blocks the expression of the lac operon which is downstream of the promoter and upstream of the transcriptional initiation site.
The operator also consists of a specific nucleotide that is recognized by the repressors which bind tightly and block the transcription.
The lac repressors have a very high affinity for the lactose, when a small amount of lactose is present, lacI binds and dissociated from the DNA operator, and frees operons from regulating the gene expression.
Such substances which cause repressors to dissociate from operators are known as inducers and the genes regulated by the repressors are known as inducible genes.
Positive Regulation of Lac Operon
Though lactose induces the expression of the lac operon, the expression level is very low, the reason for this is due to the reduced expression of the genes and it can be regulated with the presence of glucose.
Glucose is easily metabolized so it is prefeed as a source over lactose to prevent the expression of the lac operon.
The promoter for the lac operon is weak and it is poorly transcribed for induction. The binding site is present upstream from the promoter, for a protein known as CAP (catabolic activator protein).
When CAP binds it distorts the DNA which results in RNA polymerase binding in an effective manner and transcription is very much enhanced in the lac operon.
To bind the CAP must bind initially with the cAMP which increases the activating CAP and stimulates the transcription.
Thus, the cAMP and the CAP complex are referred to as positive regulators.
Lac Operon Citations
- Modeling network dynamics: the lac operon, a case study. J Cell Biol . 2003 May 12;161(3):471-6. 4;16(4):1729-1749.
- Analytical Expressions and Physics for Single-Cell mRNA Distributions of the lac Operon of E. coli. Biophys J . 2019 Aug 6;117(3):572-586.
- Stability and Hopf bifurcation analysis of lac Operon model with distributed delay and nonlinear degradation rate. Math Med Biol . 2019 Dec 4;36(4):489-512.
- Kinetic approaches to lactose operon induction and bimodality. J Theor Biol . 2013 May 21;325:62-75.
- Weak operator binding enhances simulated Lac repressor-mediated DNA looping. Biopolymers . 2013 Dec;99(12):1070-81.
- Bistability and Asynchrony in a Boolean Model of the L-arabinose Operon in Escherichia coli. Bull Math Biol . 2017 Aug;79(8):1778-1795.
- Induction of the lac promoter in the absence of DNA loops and the stoichiometry of induction. Nucleic Acids Res . 2006 Jan 23;34(2):606-12.
- Effect of lac repressor oligomerization on regulatory outcome. Mol Microbiol . 1992 Apr;6(8):963-8.