1. The lac Operon of E. Coli AMATH 882 Lecture 8, Feb. 7, 2011

2. The lac operon offers one of the simplest genetic circuits: an autoregulatory circuit (in which the product regulates the rate of expression of its own gene). An operon is a set of genes found in sequence which share a regulatory region, and so are coordinately regulated. http://www.aw-bc.com/mathews/ch26/fi26p33.gif trp operon:

3. The lac operon codes for three proteins:  -galactosidase (produced by gene lacZ)  - galactoside permease (produced by gene lacY)  - galactoside transacetylase (produced by gene lacA) http://www.science.siu.edu/microbiology/micr460/460%2520Pages/Lac.operon.html&h=313&w=478&sz=5&tbnid=NrkEQdMXcWgJ :&tbnh=82&tbnw=125&start=14&prev=/images%3Fq%3Doperon%2Blac%26hl%3Den%26lr%3D

4. Function of the lac operon: E. coli’s preferred energy source is the sugar glucose. When glucose is available, the cell maintains only very low levels of enzymes needed to metabolize other substrates (e.g. other sugars). In particular, in such a case there are relatively few copies of the enzyme  - galactosidase which breaks down lactose (milk sugar) to galacatose and glucose. http://www.indiana.edu/~ensiweb/lessons/tp.2.gif  -galactosidase

5. Production of  -galactosidase is kept low by a repressor bound to the lac operon. http://bio.winona.msus.edu/berg/3 08s04/Lec-note/21-new.htm

6. However, when switched to a lactose- rich, glucose-poor environment, the cell takes up lactose which is isomerized by  -galactosidase to allolactose (this is a second reaction catalysed by  - galactosidase) http://www.biochem.arizona.edu/classes/bioc471/pages/Lecture4/Lecture4.html  -galactosidase

7. Allolactose binds to the repressor and reduces its affinity for the regulatory site (terminology: allolactose sequesters the repressor away from the regulatory site). http://bio.winona.msus.edu/berg/3 08s04/Lec-note/21-new.htm

8. Consequently, the cell begins transcription of the lac operon. (This response happens on a timescale of minutes.) The result: increased levels of  -galactosidase, permease, and transacetylase. http://bio.winona.msus.edu/berg/3 08s04/Lec-note/21-new.htm

9. The permease mediates increased transport of lactose into the cell, while increased levels of  - galactosidase lead to increased production of allolactose (setting up a positive feedback) and also production of galactose and glucose (an energy supply). (The transacetylase is not essential for lactose metabolism. It's function as part of the operon is not understood)  -galactosidase http://bio.winona.msus.edu/berg/308s04/Lec-note/21-new.htm http://www.indiana.edu/~ensiweb/lessons/tp.2.gif

10. Remark: this is not the whole story. Transcription of the genes in the operon also requires the presence of an inducer: catabolic gene activiting protein (CAP) (also known as cAMP receptor protein (CRP)) which is constituitively present in the cell, but becomes active when bound to cyclic adenosine monophosphate (cAMP). cAMP is a "hunger signal" which varies inversely with glucose levels in the cell. http://bio.winona.msus.edu/berg/3 08s04/Lec-note/21-new.htm