In Vitro Synthesis of Curcuminoids by Type III Polyketide Synthase from Oryza sativa

Katsuyama, Yoshihiko; Matsuzawa, Miku; Funa, Nobutaka; Horinouchi, Sueharu

doi:10.1074/jbc.m707569200

Cited by 89 publications

(95 citation statements)

References 26 publications

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“…CUS then utilizes the nucleophilic water to terminate the initial polyketide chain elongation at the diketide stage (19). Cleavage of CoA from the diketide-CoAs yields b-keto acids that are used by CUS as the second extender unit to afford curcuminoids (20). Recently, the structure of CUS has been determined.…”

Section: Plant Type III Pkssmentioning

confidence: 99%

Type III polyketide synthases in natural product biosynthesis

et al. 2012

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SummaryPolyketides represent an important class of biologically active and structurally diverse compounds in nature. They are synthesized from acyl-coenzyme A substrates by polyketide synthases (PKSs). PKSs are classified into three groups: types I, II, and III. This article introduces recent studies on type III PKSs identified from plants, bacteria, and fungi, and describes the catalytic functions of these enzymes in detail. Plant type III PKSs have been widely studied, as exemplified by chalcone synthase, which plays an important role in the synthesis of plant metabolites. Bacterial type III PKSs fall into five groups, many of which were identified from Streptomyces, a genus that has been well known for its production of bioactive molecules and genetic alterability. Although it was believed that type III PKSs exist exclusively in plants and bacteria, recent fungal genome sequencing projects and biochemical studies revealed the presence of type III PKSs in filamentous fungi, which provides a new chance to study fungal secondary metabolism and synthesize ''unnatural'' natural products. Type III PKSs have been used for the biosynthesis of novel molecules through precursordirected and structure-based mutagenesis approaches.2012 IUBMB IUBMB Life, 64(4): [285][286][287][288][289][290][291][292][293][294][295] 2012

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Section: Plant Type III Pkssmentioning

confidence: 99%

Type III polyketide synthases in natural product biosynthesis

et al. 2012

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“…1E). Although its physiological function remains to be elucidated, it is remarkable that a single enzyme catalyzes the condensation of two molecules of 4-coumaroyl-CoA and one molecule of malonyl-CoA through the formation of the C 6 -C 5 4-coumaroyldiketide acid (8).…”

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confidence: 99%

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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“…Notwithstanding our efforts, however, we have not been able to detect its presence in turmeric. According to Katsuyama et al, 7) the CUS from Oryza sativa showed the highest activity in the formation of BDMC (intermediate 7 in Fig. 10) from two p-coumaroyl CoAs and one malonyl CoA, with minor but detectable activities in the formation of BDHBDMC from cinnamoyl CoA and curcumin from feruloyl CoA in vitro.…”

Section: Resultsmentioning

confidence: 99%

“…The label incorporation data obtained in this study support pathway b, proposed by Roughley and Whiting, 1) except for the timing of the introduction of the functional groups. Curcuminoid synthase (CUS), obtained from the cDNA library of Oryza sativa, 7) reportedly catalyzed the formation of curcuminoids from two phenylpropanoid CoAs and a malonyl CoA via 3-oxo-5-phenyl-pent-4-enoic acid in vitro. Our data suggest that this mechanism of curcuminoid biosynthesis works in turmeric as well.…”

Section: Resultsmentioning

confidence: 99%

“…Biotechnol. Biochem., 72 (7), 1789-1798, 2008 Recently, Katsuyama et al 7) reported that a type III polyketide synthase encoded by os07g17010 from a cDNA library of Oryza sativa synthesized curcuminoids from two phenylpropanoid CoAs and one malonyl CoA in vitro. The in vivo pathway of curcuminoid formation operating in turmeric has not however been elucidated.…”

Section: C-labeled Precursorsmentioning

confidence: 99%

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The Biosynthetic Pathway of Curcuminoid in Turmeric (Curcuma longa) as Revealed by¹³C-Labeled Precursors

Kita¹,

Imai²,

Sawada³

et al. 2008

Bioscience, Biotechnology, and Biochemistry

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In Vitro Synthesis of Curcuminoids by Type III Polyketide Synthase from Oryza sativa

Cited by 89 publications

References 26 publications

Type III polyketide synthases in natural product biosynthesis

Type III polyketide synthases in natural product biosynthesis

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

The Biosynthetic Pathway of Curcuminoid in Turmeric (Curcuma longa) as Revealed by¹³C-Labeled Precursors

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In Vitro Synthesis of Curcuminoids by Type III Polyketide Synthase from Oryza sativa

Cited by 89 publications

References 26 publications

Type III polyketide synthases in natural product biosynthesis

Type III polyketide synthases in natural product biosynthesis

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

The Biosynthetic Pathway of Curcuminoid in Turmeric (Curcuma longa) as Revealed by13C-Labeled Precursors

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The Biosynthetic Pathway of Curcuminoid in Turmeric (Curcuma longa) as Revealed by¹³C-Labeled Precursors