InterPro: IPR011141 Polyketide synthase, type III

Type III polyketide synthases include plant naringenin-chalcone synthases (CHSs) [1] and stilbene synthases (STSs) (resveratrol synthases) [2]. This group also includes CHS-related enzymes such as bibenzyl synthase (BBS) [3] and acridone synthase (ACS) [4] that share a common chemical mechanism but differ from CHS in their substrate specificity and/or in the stereochemistry of the polyketide cyclisation reaction. It also includes prokaryotic type III polyketide synthases (PKSs).

Type III polyketide synthases catalyse formation of structurally diverse polyketides. They are homodimeric iterative PKSs and contain two independent active sites each of which catalyses single or multiple condensation reactions to generate polyketides of different lengths [5]. CHS and STS are plant-specific polyketide synthases. With a starter CoA-ester they perform three sequential condensation steps with acetate units from malonyl-CoA to form a tetraketide intermediate that is folded to the ring systems specific to the different products. Each monomer subunit is capable of performing all three condensation steps, and malonyl-CoA is the direct donor of the acetate units. The structure of the Medicago sativa (Alfalfa) CHS2 has the active site architecture that defines the sequence and chemistry of multiple decarboxylation and condensation reactions [6].

CHSs (EC:2.3.1.74) are key enzymes in flavonoid assembly. They synthesize naringenin chalcone, the precursor for a large number of flavonoids. CHS is essential for formation of 4,2',4',6'-tetrahydroxychalcone, a plant secondary metabolite that sits at a critical metabolic branch point leading to the biosynthesis of anthocyanin pigments, anti-microbial phytoalexins, and flavonoid inducers of Rhizobium nodulation genes. STSs (EC:2.3.1.95) occur in a limited number of unrelated plants and synthesize the backbone of the stilbene phytoalexins that have antifungal properties and contribute to pathogen defence.

This group also contains prokaryotic type III PKSs [7]. They have been shown to be responsible for the biosynthesis of natural products such as 1,3,6,8-tetrahydroxynaphthalene (THN) (produced by RppA protein) [8] and for the formation of key components of more complex molecules such as the antimicrobial agent vancomycin (produced by DpgA protein) [9]. Streptomyces coelicolor THN synthase (THNS) is believed to be involved in the biosynthesis of the prenylated naphthoquinone cytotoxin marinone in a marine sediment-derived actinomycete [10].