Structure and function of the chalcone synthase superfamily of plant type III polyketide synthases

Abe, Ikuro; Morita, Hiroyuki

doi:10.1039/b909988n

Cited by 283 publications

(262 citation statements)

References 138 publications

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“…Recent crystallographic and site-directed mutagenesis studies on plant and bacterial type III PKSs have revealed that the functional diversity of the type III PKSs is principally derived from modifications of the active-site cavity (1,2). The amino acid sequence of O. sativa CUS shares 40-51% identity with other plant type III PKSs; 49% identity with M. sativa CHS, 51% identity with C. longa DCS, and 45% identity with C. longa CURS (Fig.…”

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“…However, Thr132, Thr197, Gly256, and Phe265, lining the active-site cavity of M. sativa CHS, are characteristically substituted with Asn, Tyr, Met, and Gly, respectively, which may account for the catalytic activity of CUS. The first three of these residues are altered in a number of functionally divergent type III PKSs and play crucial roles in controlling the substrate and product specificities of the type III PKS enzyme reactions (1,2). Indeed, recent structural analyses of Pinus sylvestris STS have demonstrated that the backbone change of the loop leads to the subtle displacement of Thr132, resulting in the rearrangement of the hydrogen bond networks including Thr132 and a nucleophilic water molecule at the active-site center (9).…”

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“…T ype III polyketide synthases (PKSs) are structurally simple, homodimeric proteins that use a single active site to produce pharmaceutically and biologically important, structurally divergent natural polyketide scaffolds (1)(2)(3). For example, chalcone synthase (CHS) and stilebene synthase (STS) catalyze the sequential condensation of 4-coumaroyl-CoA as a starter substrate with three C 2 units from malonyl-CoA, to produce the C 6 -C 3 -C 6 scaffold of naringenin chalcone, the key intermediate in flavonoid biosynthesis, and the C 6 -C 2 -C 6 scaffold of resveratrol, respectively ( Fig.…”

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Structural basis for the one-pot formation of the diarylheptanoid scaffold by curcuminoid synthase from Oryza sativa

Morita

Wanibuchi

Nii

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Curcuminoid synthase (CUS) from Oryza sativa is a plant-specific type III polyketide synthase (PKS) that catalyzes the remarkable one-pot formation of the C 6 -C 7 -C 6 diarylheptanoid scaffold of bisdemethoxycurcumin, by the condensation of two molecules of 4-coumaroyl-CoA and one molecule of malonyl-CoA. The crystal structure of O. sativa CUS was solved at 2.5-Å resolution, which revealed a unique, downward expanding active-site architecture, previously unidentified in the known type III PKSs. The large active-site cavity is long enough to accommodate the two C 6 -C 3 coumaroyl units and one malonyl unit. Furthermore, the crystal structure indicated the presence of a putative nucleophilic water molecule, which forms hydrogen bond networks with Ser351-Asn142-H 2 O-Tyr207-Glu202, neighboring the catalytic Cys174 at the active-site center. These observations suggest that CUS employs unique catalytic machinery for the one-pot formation of the C 6 -C 7 -C 6 scaffold. Thus, CUS utilizes the nucleophilic water to terminate the initial polyketide chain elongation at the diketide stage. Thioester bond cleavage of the enzyme-bound intermediate generates 4-coumaroyldiketide acid, which is then kept within the downward expanding pocket for subsequent decarboxylative condensation with the second 4-coumaroyl-CoA starter, to produce bisdemethoxycurcumin. The structure-based site-directed mutants, M265L and G274F, altered the substrate and product specificities to accept 4-hydroxyphenylpropionyl-CoA as the starter to produce tetrahydrobisdemethoxycurcumin. These findings not only provide a structural basis for the catalytic machinery of CUS but also suggest further strategies toward expanding the biosynthetic repertoire of the type III PKS enzymes.

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Structural basis for the one-pot formation of the diarylheptanoid scaffold by curcuminoid synthase from Oryza sativa

Morita

Wanibuchi

Nii

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Topologically, the catalytic triad along with Phe-216 intersect with three interconnected cavities, a CoA-binding tunnel, a coumaroylbinding pocket, and a cyclization pocket, to form the active site architecture of CHS. The active site consists of a bilobed initiation/elongation/cyclization cavity, with one lobe thought to choose the aromatic moiety of p-coumaroyl-CoA and the other housing the growing polyketide chain (Abe and Morita, 2010).…”

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Functional Promiscuity of Two Divergent Paralogs of Type III Plant Polyketide Synthases

et al. 2016

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Plants effectively defend themselves against biotic and abiotic stresses by synthesizing diverse secondary metabolites, including health-protective flavonoids. These display incredible chemical diversity and ubiquitous occurrence and confer impeccable biological and agricultural applications. Chalcone synthase (CHS), a type III plant polyketide synthase, is critical for flavonoid biosynthesis. It catalyzes acyl-coenzyme A thioesters to synthesize naringenin chalcone through a polyketidic intermediate. The functional divergence among the evolutionarily generated members of a gene family is pivotal in driving the chemical diversity. Against this backdrop, this study was aimed to functionally characterize members of the CHS gene family from Rheum emodi, an endangered and endemic high-altitude medicinal herb of northwestern Himalayas. Two full-length cDNAs (1,179 bp each), ReCHS1 and ReCHS2, encoding unique paralogs were isolated and characterized. Heterologous expression and purification in Escherichia coli, bottom-up proteomic characterization, high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry analysis, and enzyme kinetic studies using five different substrates confirmed their catalytic potential. Phylogenetic analysis revealed the existence of higher synonymous mutations in the intronless divergents of ReCHS. ReCHS2 displayed significant enzymatic efficiency (V max /K m ) with different substrates. There were significant spatial and altitudinal variations in messenger RNA transcript levels of ReCHSs correlating positively with metabolite accumulation. Furthermore, the elicitations in the form of methyl jasmonate, salicylic acid, ultraviolet B light, and wounding, chosen on the basis of identified cis-regulatory promoter elements, presented considerable differences in the transcript profiles of ReCHSs. Taken together, our results demonstrate differential propensities of CHS paralogs in terms of the accumulation of flavonoids and their relative substrate selectivities.Plants, as ground-anchored sessile creatures, invest significant amounts of energy in the production of secondary metabolites to combat environmental pressures. These metabolites often are produced through complex and highly regulated biosynthetic pathways under the influence of different enzymatic machineries. One of the important classes of secondary metabolites is phenylpropanoids. These represent a significant proportion of secondary metabolites, encompassing nearly 20% of total carbon in the terrestrial biosphere. Flavonoids exhibit remarkable chemical diversity and ubiquitous occurrence and play an important role in many aspects of plant development, like flower coloration, photoprotection, pollen development, cell wall growth, and response to stress conditions like UV light protection, herbivory, wounding, interaction with soil microbes, and defense against pathogens (Yu and Jez, 2008;Pandey et al., 2015). Apart from performing numerous imperative roles in plants, flavonoids also have been reported as poten...

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“…Genetic analyses of flower color mutants have been instrumental to the identification of several structural and regulatory genes in the species (Koes et al 2005;Ambawat et al 2013). In a large number of higher plant species, the activity of chalcone synthase displays gene redundancy and it is encoded by at least nine genes in Medicago truncatula, three in grapevine, two in maize and only one in Antirrhinum (Desnos et al 2001;Koes et al 2005;Abe and Morita 2010). The CHS gene family in Ipomoea, a genus of the Solanales order, consists of five genes: CHSA until E (Abe and Morita 2010); whereas in Petunia, twelve CHS genes have been described, although their functionality has not been accessed (Koes et al 2005).…”

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confidence: 99%

A reverse genetics approach identifies novel mutants in light responses and anthocyanin metabolism in petunia

Berenschot

Quecini

2013

Physiol Mol Biol Plants

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Flower color and plant architecture are important commercially valuable features for ornamental petunias (Petunia x hybrida Vilm.). Photoperception and light signaling are the major environmental factors controlling anthocyanin and chlorophyll biosynthesis and shadeavoidance responses in higher plants. The genetic regulators of these processes were investigated in petunia by in silico analyses and the sequence information was used to devise a reverse genetics approach to probe mutant populations. Petunia orthologs of photoreceptor, light-signaling components and anthocyanin metabolism genes were identified and investigated for functional conservation by phylogenetic and protein motif analyses. The expression profiles of photoreceptor gene families and of transcription factors regulating anthocyanin biosynthesis were obtained by bioinformatic tools. Two mutant populations, generated by an alkalyting agent and by gamma irradiation, were screened using a phenotype-independent, sequence-based method by high-throughput PCR-based assay. The strategy allowed the identification of novel mutant alleles for anthocyanin biosynthesis (CHALCONE SYNTHASE ) and regulation (PH4), and for light signaling (CONSTANS ) genes.

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Structure and function of the chalcone synthase superfamily of plant type III polyketide synthases

Cited by 283 publications

References 138 publications

Structural basis for the one-pot formation of the diarylheptanoid scaffold by curcuminoid synthase from Oryza sativa

Structural basis for the one-pot formation of the diarylheptanoid scaffold by curcuminoid synthase from Oryza sativa

Functional Promiscuity of Two Divergent Paralogs of Type III Plant Polyketide Synthases

A reverse genetics approach identifies novel mutants in light responses and anthocyanin metabolism in petunia

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