- 4-Hydroxy-3-methyl-6-(1-methyl-2-oxoalkyl)pyran-2-one Synthesis by a Type III Polyketide Synthase from Rhodospirillum centenum
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The purple photosynthetic bacterium Rhodospirillum centenum has a putative type III polyketide synthase gene (rpsA). Although rpsA was known to be transcribed during the formation of dormant cells, the reaction catalyzed by RpsA was unknown. Thus we examined the RpsA reaction in vitro, using various fatty acyl-CoAs with even numbers of carbons as starter substrates. RpsA produced tetraketide pyranones as major compounds from one C10-14 fatty acyl-CoA unit, one malonyl-CoA unit and two methylmalonyl-CoA units. We identified these products as 4-hydroxy-3-methyl-6-(1-methyl-2-oxoalkyl)pyran-2-ones by NMR analysis. RpsA is the first bacterial type III PKS that prefers to incorporate two molecules of methylmalonyl-CoA as the extender substrate. In addition, in vitro reactions with 13C-labeled malonyl-CoA revealed that RpsA produced tetraketide 6-alkyl-4-hydroxy-1,5-dimethyl-2-oxocyclohexa-3,5-diene-1-carboxylic acids from C14-20 fatty acyl-CoAs. This class of compounds is likely synthesized through aldol condensation induced by methine proton abstraction. No type III polyketide synthase that catalyzes this reaction has been reported so far. These two unusual features of RpsA extend the catalytic functions of the type III polyketide synthase family.
- Awakawa, Takayoshi,Sugai, Yoshinori,Otsutomo, Kanae,Ren, Shukun,Masuda, Shinji,Katsuyama, Yohei,Horinouchi, Sueharu,Ohnishi, Yasuo
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- The Botrytis cinerea type III polyketide synthase shows unprecedented high catalytic efficiency toward long chain acyl-CoAs
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BPKS from Botrytis cinerea is a novel type III polyketide synthase that accepts C4-C18 aliphatic acyl-CoAs and benzoyl-CoA as the starters to form pyrones, resorcylic acids and resorcinols through sequential condensation with malonyl-CoA. The catalytic efficiency (kcat/K m) of BPKS was 2.8 × 105 s-1 M -1 for palmitoyl-CoA, the highest ever reported. Substrate docking analyses addressed the unique features of BPKS such as its high activity and high specificity toward long chain acyl-CoAs.
- Jeya, Marimuthu,Kim, Tae-Su,Tiwari, Manish Kumar,Li, Jinglin,Lee, Jung-Kul,Zhao, Huimin
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p. 2864 - 2867,4
(2020/09/16)
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- Alkylresorcylic acid synthesis by type III polyketide synthases from rice Oryza sativa
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Alkylresorcinols, produced by various plants, bacteria, and fungi, are bioactive compounds possessing beneficial activities for human health, such as anti-cancer activity. In rice, they accumulate in seedlings, contributing to protection against fungi. Alkylresorcylic acids, which are carboxylated forms of alkylresorcinols, are unstable compounds and decarboxylate readily to yield alkylresorcinols. Genome mining of the rice Oryza sativa identified two type III polyketide synthases, named ARAS1 (alkylresorcylic acid synthase) and ARAS2, that catalyze the formation of alkylresorcylic acids. Both enzymes condensed fatty acyl-CoAs with three C2 units from malonyl-CoA and cyclized the resulting tetraketide intermediates via intramolecular C-2 to C-7 aldol condensation. The alkylresorcylic acids thus produced were released from the enzyme and decarboxylated non-enzymatically to yield alkylresorcinols. This is the first report on a plant type III polyketide synthase that produces tetraketide alkylresorcylic acids as major products.
- Matsuzawa, Miku,Katsuyama, Yohei,Funa, Nobutaka,Horinouchi, Sueharu
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experimental part
p. 1059 - 1067
(2011/03/20)
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- Exploiting the reaction flexibility of a type III polyketide synthase through in vitro pathway manipulation
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A synthetic metabolic pathway has been constructed in vitro consisting of the type III polyketide synthase from Streptomyces coelicolor and peroxidases from soybean and Caldariomyces fumago (chloroperoxidase). This has resulted in the synthesis of the pentaketide flaviolin and its dimeric derivative, and a wide range of pyrones and their coupled derivatives with flaviolin, as well as their halogenated derivatives. The addition of acyl-CoA oxidase to the pathway prior to the polyketide synthase resulted in unsaturated pyrone side chains, further broadening the product spectrum that can be achieved. The approach developed in this work, therefore, provides a new model to exploit biocatalysis in the synthesis of complex natural product derivatives. Copyright
- Jeong, Jae-Cheol,Srinivasan, Aravind,Grueschow, Sabine,Bach, Horacio,Sherman, David H.,Dordick, Jonathan S.
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- Enzymatic formation of long-chain polyketide pyrones by plant type III polyketide synthases
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Recombinant chalcone synthase from Scutellaria baicalensis and stilbene synthase from Arachis hypogaea accepted CoA esters of long-chain fatty acid as a starter substrate, and carried out sequential condensations with malonyl-CoA, leading to formation of triketide and tetraketide α-pyrones. Recombinant chalcone synthase (CHS) from Scutellaria baicalensis and stilbene synthase (STS) from Arachis hypogaea accepted CoA esters of long-chain fatty acid (CHS up to the C12 ester, while STS up to the C14 ester) as a starter substrate, and carried out sequential condensations with malonyl-CoA, leading to formation of triketide and tetraketide α-pyrones. Interestingly, the C6, C8, and C10 esters were kinetically favored by the enzymes over the physiological starter substrate; the k cat/KM values were 1.2- to 1.9-fold higher than that of p-coumaroyl-CoA. The catalytic diversities of the enzymes provided further mechanistic insights into the type III PKS reactions, and suggested involvement of the CHS-superfamily enzymes in the biosynthesis of long-chain alkyl polyphenols such as urushiol and ginkgolic acid in plants.
- Abe, Ikuro,Watanabe, Tatsuya,Noguchi, Hiroshi
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p. 2447 - 2453
(2007/10/03)
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- Substituted 2-Pyrones, 2-Pyridones, and Other Congeners of Elasnin as Potential Agents for the Treatment of Chronic Obstructive Lung Diseases
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Several congeners of elasnin (I) have been synthesized and shown to inhibit human leukocyte elastase (HLE).The C-3 alkyl substituted 2-pyrones 11 and 12 were found to be most inhibitors of the enzyme.These compounds are highly specific in their inhibitory
- Groutas, William C.,Stanga, Michael A.,Brubaker, Michael J.,Huang, Tien L.,Moi, Min K.,Carroll, Robert T.
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p. 1106 - 1109
(2007/10/02)
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- A VERY SIMPLE SYTHESIS OF NATURAL SATURATED δ-SUBSTITUTED δ-LACTONES. THE PHEROMONE OF Vespa orientalis
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Very facile syntheses of racemic massoia lacton and the pheromone of Veapa orientialis have been achieved starting from dehydroacetic acid.
- Bacardit, Ramon,Moreno-Manas, Marcial
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