11/17/11
Regulation of metabolism occurs at Gene regulation in bacteria two levels:
(a) Regulation of enzyme (b) Regulation of enzyme activity production – Adjusting the activity of Precursor Today’s Topics: Feedback metabolic enzymes already inhibition Enzyme 1 Gene 1 • Transcriptional control present Enzyme 2 Gene 2 Regulation – Cells adjust to their environment • How? of gene expression by turning genes on and off – Regulating the genes Enzyme 3 Gene 3 • The operon concept – encoding the metabolic Enzyme 4 Gene 4 – Operators, Promoters, enzymes – Enzyme 5 Gene 5 Repressors, Activators • How? • Repressible operons (e.g. trp) Tryptophan • Inducible operons (e.g. lac) 18 Nov 2011
In bacteria, related genes are often clustered into Types of Regulated Genes Operons
• Constitutive genes are always expressed P R P O 1 2 3 • Tend to be vital for basic cell functions (often called “housekeeping genes”) Operons have: 1. Several genes for metabolic enzymes • Inducible genes are normally off, but can be turned 2. One promoter on when substrate is present • Common for catabolic enzymes (i.e. for the utilization of 3. An operator, or control site particular resources) (“on-off” switch)
• Repressible genes are normally on, but can be 4. A separate gene that makes a repressor or turned off when the end product is abundant activator protein that binds to the operator • Common for anabolic enzymes
The trp Operon
Controlled by a single Terminology promoter and operator • Promoters and Operators are DNA sequences 5 genes: E, D, C, B, A upstream of genes
• Repressors and Activators are proteins that bind to DNA and control transcription.
• Co-repressors and Inducers are small “effector” molecules that bind to repressors or activators
Same order as enzymes for trp synthesis
1 11/17/11
The trp operon: regulated synthesis Active repressor can bind to operator and of repressible enzymes block transcription
DNA Regulatory trp operon No RNA made gene Promoter Genes of operon DNA trpR trpE trpD trpC trpB trpA Operator RNA mRNA mRNA 3! polymerase mRNA 5! 5! E D C B A Protein Polypeptides that make up Protein Active enzymes for tryptophan synthesis repressor Figure 18.3 Tryptophan (corepressor) Tryptophan absent ! repressor inactive ! operon “on” Tryptophan present ! repressor active ! operon “off” Figure 18.3
• The lac operon: regulated synthesis of Tryptophan changes the shape of the inducible enzymes repressor protein so it can bind DNA Promoter Regulatory Operator gene DNA lacl lacZ
No RNA made 3! RNA mRNA polymerase 5!
Active Protein repressor
(a) Lactose absent, repressor active, operon off. The lac repressor is innately active, and in the absence of lactose it switches off the operon by binding to the operator. Figure 18.4
lac operon
DNA lacl lacz lacY lacA
RNA polymerase 3! mRNA mRNA 5'5! 5!
Protein "-Galactosidase Permease Transacetylase
Allolactose Inactive (inducer) repressor
(b) Lactose present, repressor inactive, operon on. Allolactose, an isomer of lactose, derepresses the operon by inactivating the repressor. In this way, the enzymes for lactose utilization are induced. Figure 18.4
2