Plants, polyketide production

Type III polyketide synthases are particularly relevant to this chapter because they catalyze the formation of phenolic compounds. This group of polyketide synthases consists of CHSs, stilbene synthase (STS), and curcuminoid synthase (CUS), which perform decarboxylative condensations between a starter unit, either p-coumaroyl-CoA 19 or cinnamoyl-CoA 18, and an extender unit, malonyl-CoA 10. CHS, STS, and CUS convert the substrate molecules into flavo-noids (Cg-Cs-Cg), stilbenoids 8 (Cg-C2-Cg), and curcuminoids 9 (Cg-C7-C6), respectively [59]. Stilbenoids 8 and curcuminoids 9 are out of the scope of this chapter but possess medicinal properties as well resveratrol is a well-known stilbenoid 8 associated with longevity, and curcumin is a common curcuminoid 9 that is responsible for the yellow color in turmeric and can be utilized as a natural pigment possessing antioxidant and anti-inflammatory properties [60-63]. For an in-depth treatment of plant polyketide production in microbes, the reader is directed to a recent comprehensive review by Boghigian et al. [64]. 

Bender, C.L., Rangaswamy, V., Loper J. Polyketide production by plant associated pseudomonads. Annu Rev Phytopathol 1999 37 175-196. 

Chalcone synthase (CHS), the first plant natural product polyketide synthase (PKS) to be characterized at the molecular level (39), catalyzes the condensation of 4-coumaroyl-CoA with three molecules of malonyl-CoA to afford naringenin chalcone, a precursor of the major classes of plant flavonoids. The cloning of a novel type III pentaketide chromone synthase (PCS) from aloe (Aloe arborescens, Liliaceae) rich in aromatic polyketides, especially quinones such as aloe-emodin and emodin, resulted in... 

Diketide products of this super family of plant polyketide synthases probably include acridones and also phenylphenalenones such as the aglycone of haemocorin (69), which may be formed from one malonyl-CoA and two phenylpropanyl-CoA units (Figure 8). The proposed derivation of 69 via a diarylheptanoid related to curcumin (70) was... 

This group of enzymes directs flux into the major classes of plant natural products e.g. polyketides (including flavonoids), alkaloids and terpenes. The initially formed scaffold molecules then enter different branch pathways as precursors for further downstream modifications. 

Many polyketide-derived plant natural products originate in part from acetyl CoA via malonyl CoA (Fig. 1). For example, the key reaction in flavonoid biosynthesis, catalyzed by chalcone synthase (CHS) (Fig. 2), combines a phenylpro-panoid-derived moiety, 4-coumaroyl CoA, with three molecules of malonyl CoA. Although acetyl CoA carboxylase, the enzyme forming malonyl CoA, is essentially an enzyme of primary metabohsm (Fig. 1), it is often co-regulated with the enzymes of plant polyketide biosynthesis [8]. 

Recently, a new polyketide biosynthetic pathway in bacteria that parallels the well studied plant PKSs has been discovered that can assemble small aromatic metabolites.8,9 These type III PKSs10 are members of the chalcone synthase (CHS) and stilbene synthase (STS) family of PKSs previously thought to be restricted to plants.11 The best studied type III PKS is CHS. Physiologically, CHS catalyzes the biosynthesis of 4,2, 4, 6 -tetrahydroxychalcone (chalcone). Moreover, in some organisms CHS works in concert with chalcone reductase (CHR) to produce 4,2 ,4 -trihydroxychalcone (deoxychalcone) (Fig. 12.1). Both natural products constitute plant secondary metabolites that are used as precursors for the biosynthesis of anthocyanin pigments, anti-microbial phytoalexins, and chemical inducers of Rhizobium nodulation genes.12... 

The second largest class of compounds reported from macroalgae is the polyketides, which comprise approximately a quarter of known algal compounds (Blunt et al. 2007). Polyketides are polymers of acetate (C2) and occasionally propionate (C3) and are very similar to fatty acids in their biosynthetic origin. Polyketides can be found in plants, animals, bacteria, and fungi. With a range of activities as broad as their structures, the polyketides are a diverse family of natural products classified based upon the polyketide synthases (PKSs) responsible for their biosynthesis, primarily type I and type II. 

Facciotti, D. Metz, J.G. Lassner, M. (1998) Polyketide synthesis graes of marine microbe and production of polyunsaturated fatty acids and PUFA-containing plant oils with transgenic plants. PCT Int. Appl. 10 Dec. to Calgene LLC Co) Chem. Abstr., 1999,130, 62050. 

PKSs are characterized by their ability to catalyze the formation of polyketide chains from the sequential condensation of acetate units from malonate thioesters. In plants they produce a range of natural products with varied in vivo and pharmacological properties. PKSs of particular note include acridone synthase, bibenzyl synthase, 2-pyrone synthase, and stilbene synthase (STS). STS forms resveratrol, a plant defense compound of much interest with regard to human health. STS shares high sequence identity with CHS, and is considered to have evolved from CHS more than once. ° Knowledge of the molecular structure of the CHS-like enzymes has allowed direct engineering of CHS and STS to alter their catalytic activities, including the number of condensations carried out (reviewed in Refs. 46, 51, 52). These reviews also present extensive, and superbly illustrated, discussions of CHS enzyme structure and reaction mechanism. 

---