Microbial Genetics (Micr340) Lecture 16 Global Regulatory Mechanisms Note: a hand-out for Lecture 15 was uploaded into course web folder

Global regulation Global regulatory mechanisms: regulatory systems within cells that simultaneously regulate numerous operons in response to major changes in the environment These systems respond to these factors: Nutrient limitation Growth limitation Stress

Catabolite-sensitive operons Regulon: a large number of operons that are controlled by a single regulatory protein. Catabolites: smaller molecules resulting from the metabolic breakdown (catabolism) of larger molecules. Catabolite repression: a mechanism for ensuring that the cell will preferentially use the best carbon and energy source available.

Preferential utilization

cAMP and cAMP-Binding Protein cAMP: cyclic AMP is similar to AMP, except the phosphate is attached to both 5’- and 3’ hydroxyl groups of the sugar. In E. coli, there is a cAMP-dependent regulatory system that controls preferential utilization of sugar sources CAP (catabolite gene activator protein), also known as CRP (cAMP receptor protein), is the global activator of catabolite sensitive operons

Glucose inhibits cAMP synthesis and uptake of other sugars

In absence of Glucose……. Lactose

Regulation of lac by CAP-cAMP

CAP-cAMP and other opeons gal operon

CAP-cAMP and other opeons ara operon

Nitrogen nutrient Nitrogen is a component of many biological molecules thus is an essential nutrient source Bacteria could use both inorganic (ammonia and nitrate) and organic nitrogen sources Some bacteria can even use (fix) atmospheric nitrogen (N 2 ), unique on earth.

Pathways of nitrogen assimilation Ammonia is the preferred source of nitrogen for most bacteria Other forms of nitrogen must be reduced to ammonia before they can be used in a process called assimilatory reduction The process of ammonia being integrated (assimilated) into an organic compound of biosynthetic pathways is called nitrogen assimilation

Pathways of nitrogen assimilation

Regulation of Ntr operons

Two-component system

The glnA-ntrB-ntrC operon of E. coli

Sigma factors define promoters

Model of Activation of p 2 promoter