Lac operon

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The lac operon is a DNA sequence that governs the production of enzymes for metabolizing lactose in bacteria such as E. coli. In the absence of lactose, the lac repressor substance binds to the operator (a part of the DNA sequence), inhibiting the production of three enzymes. Lactose, however, represses/inhibits the repressor, allowing the enzymes to be produced. When the mRNA of the lac operon is transcribed, a polycistronic mRNA, three enzymes will be produced by ribosomes: β-galactosidase, β-galactoside permease and β-galactoside transacetylase.

The lac operon is considered the canonical example of prokaryotic gene regulation.

Discovery

Figure 1: Monod Growth Curve

It is traditional to give three letter codes for genes; "Lac" refers to a group of three enzymes for metabolism of the sugar lactose that are together as a group on the bacterial chromosome. The experimental system used by Jacob and Monod was a common bacterium, E. coli, but the basic regulatory concept (described below) that was discovered by Jacob and Monod is fundamental to cellularular regulation for all organisms. The key idea is that E. coli does not bother to waste energy making such enzymes if there is no need to metabolize lactose, such as when other sugars like glucose are available. How do bacteria "know" when to activate certain genes in response to metabolic needs?

During World War II, Monod was testing the effects of combinations of sugars as nutrient sources for E._coli. He found that bacteria grown with two different sugars often displayed two phases of growth. For example, if glucose and lactose were both provided, glucose would be metabolized first (growth phase I, see Figure 1) and then lactose (growth phase II). But why was there a delay between the two growth phases?

The operon

Figure 2: Lac operon in detail

When the glucose has been removed from the culture medium at the end of growth phase I, the bacteria start to make an activator protein. After a short period of time, the level of the activator proteins builds up inside the cells to levels that can allow lactose to be metabolized. There is also a second level of regulation. The bacteria also make a specific repressor protein that prevents the cells from making the enzymes that are needed to metabolize lactose. However, when lactose is present it binds to the inhibitory protein and prevents the inhibitory protein from doing its job (this is an example of allosteric regulation). This dual regulation causes the lactose metabolism enzymes to be made only when there is no glucose available AND when there is lactose available. The basic molecular trick is that this regulation is accomplished by protein molecules that bind to specific parts of the Lac operon (see Figure 2). Such regulatory proteins are called transcriptional control proteins or transcription factors and are fundamental to the regulation of all biological cells.