Acetyl-CoA synthetase

It is in the ligase class of enzymes, meaning that it catalyzes the formation of a new chemical bond between two large molecules.

The complete reaction with all the substrates and products included is: Once acetyl-CoA is formed it can be used in the TCA cycle in aerobic respiration to produce energy and electron carriers.

First, AMP must be bound by the enzyme to cause a conformational change in the active site, which allows the reaction to take place.

[5] The ACS1 form of acetyl-CoA synthetase is encoded by the gene facA, which is activated by acetate and deactivated by glucose.

[6] The three dimensional structure of the asymmetric ACS (RCSB PDB ID number: 1PG3) reveals that it is composed of two subunits.

During chromatography in the process to isolate the enzyme, the subunits came out individually and the total structure was determined separately.

The unit cell values and angles are provided in the following table: The role of the ACS enzyme is to combine acetate and Coenzyme A to form acetyl-CoA, however its significance is much larger.

It has been shown that downregulation of the acs gene in the hippocampal region of mice results in lower levels of histone acetylation, but also impairs the long-term spatial memory of the animal.

When the gene is present, the cells are able to take in acetate as a food source to convert it to Acetyl-CoA during stressed conditions.

In the cases of advanced carcinoma tumors, the genes for this enzyme were down regulated and indicated a poor 5-year survival rate.

[10] Expression of the enzyme has also been linked to the development of metastatic tumor nodes, leading to a poor survival rate in patients with renal cell carcinomas.

[2] The exact location of the lysine residue varies between species, occurring at Lys-642 in humans, but is always present in the active site of the enzyme.

[3] In addition to sirtuins, protein deacetylase (AcuC) also can modify acetyl-CoA synthetase at a lysine residue.

Without correct acetylation, DNA cannot condense into chromatin properly, which inevitably results in transcriptional errors.

By overexpressing the acs gene, and using acetate as a feedstock, the production of fatty acids (FAs) may be increased.

These fatty acids could then be used as a biofuel after being separated from the media, requiring further processing (transesterification) to yield usable biodiesel fuel.

Removing the need for further processing prior to obtaining a usable fuel product in Diesel engines.

3D structure of ACS (1PG3) using PyMol software. [ 8 ]
Axial view of ACS (1PG3) showing ligands bound to active site. Ligands used for crystallization (in image) are adenosine-5'-propylphosphate, CoA and ethanediol.
FAEE (C12) produced using Keasling biosynthetic pathway in engineered E. coli (A2A). Different types possible depending on number of acetyl-CoA units incorporated (result in even number chains).
Representative fatty acid molecule (palmitic acid, C16)
Transesterification of fatty acid to ester mechanism
Regulation changes to E. coli for production of FAEE from acetate.