Lactose Operon Overview
Jacob and Monod 1961 proposed the operon model based on their studies of the lactose (lac) operon in E. coli for which they were awarded the Nobel Prize. The lac operon is a negative control system consisting of a promoter (P), an operator (O), and three structural genes, lacZ, lacY, and lacA, encoding the enzyme β-galactosidase, β-galactoside permease, and β—galactoside transacetylase, respectively.
The lac operon of E. coli contains genes involved in lactose metabolism. It’s expressed only when lactose is present, and glucose is absent. Two regulators turn the operon “on” and “off” in response to lactose and glucose levels: the lac repressor and catabolite activator protein (CAP).
The lac repressor acts as a lactose sensor. It normally blocks transcription of the operon but stops acting as a repressor when lactose is present. The lac repressor senses lactose indirectly, through its isomer allolactose. Catabolite activator protein (CAP) acts as a glucose sensor. It activates transcription of the operon, but only when glucose levels are low. CAP senses glucose indirectly, through the “hunger signal” molecule cAMP.
The lac Operon
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Functions of lac operon genes
- β-galactosidase gene codes for a β-galactosidase protein that breaks up lactose into galactose and glucose and it catalyzes the isomerization of lactose into allolactose.
- β-galactoside permease codes for a permease protein that pumps lactose into the cell.
- β-galactoside transacetylase codes for a transacetylase protein, an enzyme that transfers acetyl group from acetyl-CoA to β-galactosides. It is not necessary for lactose metabolism.

What makes the lac operon turn on?
- E. coli can break down lactose, but it’s not their favorite fuel. Glucose requires fewer steps and less energy to break down than lactose. However, if lactose is the only sugar available, E. coli will use it as an energy source. To use lactose, the bacteria must express the lac operon genes, which encode key enzymes for lactose uptake and metabolism. To be as efficient as possible, E. coli should express the lac operon only when two conditions are met: Lactose is available, and Glucose is not available
- How are levels of lactose and glucose detected, and how do changes in levels affect lac operon transcription? Two regulatory proteins are involved:
- One, the lac repressor, acts as a lactose sensor.
- The other, catabolite activator protein (CAP), acts as a glucose sensor.
- These proteins bind to the DNA of the lac operon and regulate its transcription based on lactose and glucose levels.