Synthesis of 4,4-Disubstituted L-Glutamic Acids by Enzymatic Transamination

Hélaine, Virgil; Rossi, Joël; Gefflaut, Thierry; Alaux, Sébastien; Bolte, Jean

doi:10.1002/1615-4169(200108)343:6/7<692::aid-adsc692>3.3.co;2-y

Cited by 10 publications

(16 citation statements)

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“…The fastest interconversion appears to be between the cyclic and acyclic ketone forms of zymonic acid (ZCK and ZOK) on the subsecond time scale. This rate of interconversion increases with increasing pH, which has caused the mixture of these two substances to be misidentified as a single substance in previous literature. − The slower kinetic interconversions in water indicate the direct transition from an enol to a geminal diol (ZCE to ZCD) without a ketone intermediate. A kinetic fit was performed that reinforces the validity of this observation.…”

Section: Discussionmentioning

confidence: 99%

“…At equilibrium under low pH conditions, we detect and assign five different forms of pyruvic acid dimers in solution and investigate the mechanisms of their interconversion. Our higher resolution NMR work across a broader pH range allows for the differentiation of quickly exchanging species that were assigned to single components in most previous works. − We report identification and characterization of the pyruvic acid chemical dimerization products followed by a study of the kinetics of interconversion. Finally, potential mechanisms are discussed for the novel interconversions that are observed.…”

Section: Introductionmentioning

confidence: 97%

“…Later studies are split between work examining metal catalysis − and biological processes. − Zymonic acid was identified as a metabolite in yeast, only to be shown to be a contaminant from pyruvic acid used, and an incorrect structure was first reported. , A number of other papers have discussed the detection or role of parapyruvic and zymonic acid in various biological contexts, including detection from living tissues and interactions with enzymes. − Interestingly, parapyruvic acid has been observed in meteorites alongside pyruvic acid and discussed in the context of the origin of life . There are several papers discussing the spontaneous formation of zymonic and parapyruvic acids from pyruvic acid under different conditions, which suggest that these molecules exist as contaminants in other experiments. ,− Because these dimerization products are formed relatively easily, it is somewhat unclear whether previous detections of zymonic and parapyruvic acids are artifacts of the analytical techniques that were used.…”

Section: Introductionmentioning

confidence: 99%

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Chemical Equilibria and Kinetics in Aqueous Solutions of Zymonic Acid

et al. 2016

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The chemistry of pyruvic acid is of great interest due to its essential role in metabolism for all life and its role in atmospheric chemistry. Pyruvic acid under a wide range of conditions, including normal storage conditions, will spontaneously dimerize to form zymonic acid. We isolated zymonic acid and, using a variety of 1D and 2D NMR techniques, identified it as a single structure as a solid or dissolved in DMSO. When in aqueous solution, however, we identified a mixture of five different tautomers and hydrates in equilibrium with each other with no single dominant form. The kinetics of this conversion were studied in situ via NMR. The reactivity of the tautomers and hydrates in aqueous solution is investigated and discussed in terms of aqueous reaction mechanisms. There is strong evidence for a direct, reversible conversion from an enol to a geminal diol without passing through a ketone intermediate, which implies the reversible addition of water across a double bond under ambient conditions. Additionally, there is evidence for a base catalyzed lactone ring formation, which is in essence a base catalyzed esterification reaction. The equilibrium between pyruvic acid and its oligomers in aqueous solution is of consequence in the natural environment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Chemical Equilibria and Kinetics in Aqueous Solutions of Zymonic Acid

et al. 2016

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“…The synthesis of HMOG has been previously known and updated 11 and appears to be the obvious starting point yet attempting to access the condensation product is not straightforward. Acidification of HMOG is known to facilitate a lactonization reaction forming an isotetronic acid derivative called zymonic acid 12 (Scheme 2).…”

Section: Resultsmentioning

confidence: 99%

The Pyruvate Aldol Condensation Product: A Metabolite that Escaped Synthetic Preparation for Over a Century

Rios

Bera²,

Moreno³

et al. 2020

Preprint

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<p>The homo-aldol condensation product of pyruvate, <a>2-methyl-4-oxopent-2-enedioic acid (OMPD) </a>has been recently implicated as a catabolic intermediate in the bacterial degradation of lignin and previously identified from other biological sources in reports ranging over sixty years. Yet, while a preparation of the pyruvate aldol-product precursor, 4-hydroxy-4-methyl-2-oxoglutaric acid (HMOG) was first reported in 1901, there has not been a complete published synthesis of OMPD. Analysis of reaction mixtures have helped identify that it is zymonic acid, the lactone of HMOG, that is the direct precursor to OMPD. The reaction appears to proceed through an acid or base mediated ring opening that does not involve formal lactone hydrolysis. In addition to a preparative protocol we provide a proposed mechanism for the formation of methylsuccinic acid that arises from the non-oxidative decarboxylation of OMPD. Lastly, we report on the relative stability of the possible isomers of the condensation product and find that at all pH values, Z-OMPD is the most abundant.</p>

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“…Since the α‐keto acid precursor of 12 can be obtained by an aldol condensation of two molecules of pyruvic acid, we speculated that CghB might be involved in the formation of 12 . To test this hypothesis, we synthesized 12 chemically by dimerizing pyruvic acid under a basic condition in aqueous solution, then transaminated the product with a glutamic oxalacetic transaminase using cysteinesulfinic acid as an amino group donor to obtain 12 and its diastereomers . Then, those compounds were fed to the cghB knockout strain of CGKW14, an engineered C. globosum strain capable of site‐specific homologous recombination .…”

Section: Detailed Biosynthetic Pathways Of Natural Productsmentioning

confidence: 99%

Elucidation of Biosynthetic Pathways of Natural Products

Kishimoto

Tsunematsu

Sato

et al. 2017

The Chemical Record

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During the last decade, we have revealed biosynthetic pathways responsible for the formation of important and chemically complex natural products isolated from various organisms through genetic manipulation. Detailed in vivo and in vitro characterizations enabled elucidation of unexpected mechanisms of secondary metabolite biosynthesis. This personal account focuses on our recent efforts in identifying the genes responsible for the biosynthesis of spirotryprostatin, aspoquinolone, Sch 210972, pyranonigrin, fumagillin and pseurotin. We exploit heterologous reconstitution of biosynthetic pathways of interest in our study. In particular, extensive involvement of oxidation reactions is discussed. Heterologous hosts employed here are Saccharomyces cerevisiae, Aspergillus nidulans and A. niger that can also be used to prepare biosynthetic intermediates and product analogs by engineering the biosynthetic pathways using the knowledge obtained by detailed characterizations of the enzymes. (998 char.).

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Synthesis of 4,4-Disubstituted L-Glutamic Acids by Enzymatic Transamination

Cited by 10 publications

References 0 publications

Chemical Equilibria and Kinetics in Aqueous Solutions of Zymonic Acid

Chemical Equilibria and Kinetics in Aqueous Solutions of Zymonic Acid

The Pyruvate Aldol Condensation Product: A Metabolite that Escaped Synthetic Preparation for Over a Century

Elucidation of Biosynthetic Pathways of Natural Products

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