Question

In what ways is polyketide biosynthesis similar to fatty acid biosynthesis, and in what ways are they different?

Answer 1

Polyketides are synthesized by sequential reactions catalysed by a collection of enzyme activities called polyketide synthases (PKSs). These are large multienzyme protein complexes that contain a coordinated group of active sites. The biosynthesis occurs in a stepwise manner from simple 2-, 3-, 4-carbon building blocks such as acetyl-CoA, propionyl CoA, butyryl-CoA and their activated derivatives, malonyl-, methylmalonyl- and ethylmalonyl-CoA.

The key chain-building step of polyketide biosyhnthesis is a decarboxylative condensation analogous to the chain elongation step of classical fatty acid biosynthesis.Unlike fatty acid biosynthesis, however, in which each successive chain elongation step is followed by a fixed sequence of ketoreduction, dehydration and enoyl reduction as shown above, the individual chain elongation intermediates of polyketide biosynthesis undergo all, some, or none of these functional group modifications, resulting in a striking level of chemical complexiyty in the products. Additional degrees of complexity arise from the use of different starter units and chain elongation units as well as the generation of new stereo-isomers.