Kynurenine as an Intermediate in the Formation of Nicotinic Acid from Tryptophane by Neurospora

Beadle, G. W.; Mitchell, Herschel K.; Nyc, Joseph F.

doi:10.1073/pnas.33.6.155

Cited by 168 publications

(57 citation statements)

References 2 publications

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“…The Dixon plot also showed that the inhibition is competitive ( Figure 5A). Notably, we found that TAA1 could also use Kyn as a substrate in vitro to produce kynurenic acid (KYNA), a direct metabolite of Kyn in animals (Beadle et al, 1947) ( Figure 5C). This result suggests that, like Trp, Kyn is a TAA1 substrate.…”

Section: Kyn Is a Potent Inhibitor Of Taa1/tar Aminotransferasesmentioning

confidence: 99%

A Small-Molecule Screen Identifiesl-Kynurenine as a Competitive Inhibitor of TAA1/TAR Activity in Ethylene-Directed Auxin Biosynthesis and Root Growth inArabidopsis

et al. 2011

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The interactions between phytohormones are crucial for plants to adapt to complex environmental changes. One example is the ethylene-regulated local auxin biosynthesis in roots, which partly contributes to ethylene-directed root development and gravitropism. Using a chemical biology approach, we identified a small molecule, L-kynurenine (Kyn), which effectively inhibited ethylene responses in Arabidopsis thaliana root tissues. Kyn application repressed nuclear accumulation of the ETHYLENE INSENSITIVE3 (EIN3) transcription factor. Moreover, Kyn application decreased ethylene-induced auxin biosynthesis in roots, and TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS1/TRYPTOPHAN AMINOTRANSFERASE RELATEDs (TAA1/TARs), the key enzymes in the indole-3-pyruvic acid pathway of auxin biosynthesis, were identified as the molecular targets of Kyn. Further biochemical and phenotypic analyses revealed that Kyn, being an alternate substrate, competitively inhibits TAA1/TAR activity, and Kyn treatment mimicked the loss of TAA1/TAR functions. Molecular modeling and sequence alignments suggested that Kyn effectively and selectively binds to the substrate pocket of TAA1/TAR proteins but not those of other families of aminotransferases. To elucidate the destabilizing effect of Kyn on EIN3, we further found that auxin enhanced EIN3 nuclear accumulation in an EIN3 BINDING F-BOX PROTEIN1 (EBF1)/EBF2-dependent manner, suggesting the existence of a positive feedback loop between auxin biosynthesis and ethylene signaling. Thus, our study not only reveals a new level of interactions between ethylene and auxin pathways but also offers an efficient method to explore and exploit TAA1/TAR-dependent auxin biosynthesis.

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Section: Kyn Is a Potent Inhibitor Of Taa1/tar Aminotransferasesmentioning

confidence: 99%

A Small-Molecule Screen Identifiesl-Kynurenine as a Competitive Inhibitor of TAA1/TAR Activity in Ethylene-Directed Auxin Biosynthesis and Root Growth inArabidopsis

et al. 2011

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“…[1] One of the functions of IDO in cells is the cleavage of the indole 2,3-double bond of (S)-tryptophan (1), using superoxide in the presence of free-radical generating systems, such as ascorbic acid and methylene blue. The product of this oxidative cleavage is (S)-N-formylkynurenine (2), which is subsequently hydrolyzed by a formamidase enzyme to give (S)-kynurenine (3, Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

“…[2] The kynurenine pathway contains a number of interesting enzymes that catalyze chemical reactions which are infrequently found in metabolism. Consequently, many of these transformations are still mechanistically poorly understood, such as the aforementioned IDO-catalyzed oxidative cleavage of tryptophan (1 !…”

Section: Introductionmentioning

confidence: 99%

Transition Metal‐Catalyzed Synthesis of Novel Biologically Relevant Tryptophan Analogues

et al. 2004

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A synthetic approach to the synthesis of novel tryptophan derivatives and benzofuran-containing amino acids is detailed. The sequence starts from enzymatically resolved enantiopure acetylene-containing amino acids, of which the acetylene function can be efficiently transformed into the targeted 2-substited indole and benzofuran moieties via Sonogashira-type coupling and metal-catalyzed cyclization.

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“…As a precursor-product relationship between tryptophan and nicotinic acid and the nicotinyl coenzymes has been demonstrated in higher animals (Chaykin, 1967), fungi (Beadle et al, 1947;Ahmad & Moat, 1966) and certain bacteria (Wilson & Henderson, 1963;Lingens & Vollprecht, 1964;Lingens et al, 1966), it is evident that a common path- way provides the precursor(s) needed for the biosynthesis of these diverse metabolic products (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Phenoxazinone Biosynthesis: Accumulation of a Precursor, 4-Methyl-3-hydroxyanthranilic Acid, by Mutants of Streptomyces parvulus

Troost

Katz

1979

Journal of General Microbiology

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Mutants of Streptomyces parvulus that are blocked in the synthesis of the phenoxazinonecontaining antibiotic, actinomycin, were isolated by the ' agar piece ' method (after ultraviolet irradiation or treatment with 8-methoxypsoralen plus near-ultraviolet light). Radiolabelling experiments in conjunction with paper, thin-layer and column chromatography revealed that 4-methyl-3-hydroxyanthranilic acid (MHA) is a major metabolite accumulated by these mutants. Studies in vitro and in vivo provided evidence that MHA is a precursor of the phenoxazinone chromophore, actinocin. Normally MHA does not accumulate during growth or antibiotic synthesis by the parental strains. Protoplasts derived from the mutant strain AM5 synthesized MHA in significant amounts. A scheme is proposed for the biosynthesis of actinomycin D that accounts for the accumulation of MHA by the mutants.

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Kynurenine as an Intermediate in the Formation of Nicotinic Acid from Tryptophane by Neurospora

Cited by 168 publications

References 2 publications

A Small-Molecule Screen Identifiesl-Kynurenine as a Competitive Inhibitor of TAA1/TAR Activity in Ethylene-Directed Auxin Biosynthesis and Root Growth inArabidopsis

A Small-Molecule Screen Identifiesl-Kynurenine as a Competitive Inhibitor of TAA1/TAR Activity in Ethylene-Directed Auxin Biosynthesis and Root Growth inArabidopsis

Transition Metal‐Catalyzed Synthesis of Novel Biologically Relevant Tryptophan Analogues

Phenoxazinone Biosynthesis: Accumulation of a Precursor, 4-Methyl-3-hydroxyanthranilic Acid, by Mutants of Streptomyces parvulus

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