Type III PKSs are associated with the production of chalcones, a class of organic compounds found mainly in plants as natural defense mechanisms and as synthetic intermediates.

[6] Each monomer possesses a β-keto synthase (KS) activity that catalyzes the sequential head to tail incorporation of two-carbon acetate units into a growing polyketide chain.

CHS contains a five layer αβαβα core, a location of the active site and dimerization interface that is highly similar to thiolase-fold containing enzymes.

The dimerization interface contains both hydrophobic and hydrophilic residues and is generally flat except for a pair of N-terminal helices that lay entwined across the top.

Therefore, the active site is buried except for a 16 Å CoA-binding tunnel that connects the catalytic surface to the outer surrounding milieu.

Phe215 and Phe265 are two other important amino acids that act as “gatekeepers” to block the lower protein of the opening between the CoA-binding tunnel and the active site cavity.

[13] Further investigation of the phenomenon indicated that the downregulation was due to post-transcriptional inhibition of the chalcone synthase gene expression via an increased rate of messenger RNA degradation.

[14] CHS, as the first committed step in the flavonoid pathway, facilitate production of flavanoids, isoflavonoid-type phytoalexins and other metabolites to protect the plant from stress.

Being aromatic compounds, flavonoids strongly absorb UV light through a photoreceptor-mediated mechanism which effectively protects the plants from DNA damage.

CHS is involved in a broader, more general phenylpropanoid pathway which serve as precursors to a range of plant metabolites important to human health such as antioxidants, anti-inflammatory agents, antiallergens, and even antioncogenic products.

These divergent enzymes differ from CHS in their preference for starter molecules, the number of acetyl additions (often through malonyl-CoA) and even in the mechanism of ring formation used to cyclize identical polyketide intermediates.