- Monatin and its stereoisomers: Chemoenzymatic synthesis and taste properties
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The sweet natural compound monatin 1 has two stereogenic centres and the (2S,4S) absolute configuration has been attributed to the natural isomer. We obtained all four stereoisomers as pure compounds by a six-step synthetic sequence. The stereogenic centre at C-4 was introduced stereoselectively by a regio- and enantiospecific enzymatic hydrolysis of the racemic ethyl dicarboxylate 4 using a protease from Aspergillus oryzae. The absolute configuration of the intermediate products was assigned by X-ray diffraction of chiral derivatives. The stereogenic centre at C-2 was introduced non-specifically, and the resulting diastereomeric mixtures were separated by RP-HPLC. The absolute configurations of the final products were established by comparing retention times on a chiral HPLC column with those of known samples. The four stereoisomers were submitted to tasting trials and three of them, particularly the (2R,4R) isomer, were found to be intensely sweet. A sample of natural monatin analysed under the same conditions is shown to contain all the four stereoisomers. The relative stereoisomeric content in the plant, as well as the possible isomerisation of the chiral centres during extraction and manipulation of monatin samples, are important points that need to be clarified by extensive analysis of the natural extracts. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.
- Bassoli, Angela,Borgonovo, Gigliola,Busnelli, Gilberto,Morini, Gabriella,Drew, Michael G. B.
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Read Online
- Polypeptides and biosynthetic pathways
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Methods and compositions that can be used to make monatin from glucose, tryptophan, indole-3-lactic acid, indole-3-pyruvate, and 2-hydroxy 2-(iridol-3-ylmethyl)-4-keto glutaric acid, are provided. Methods are also disclosed for producing the indole-3-pyruvate and 2-hydroxy 2-(indol-3ylmethyl)-4-keto glutaric acid intermediates. Compositions provided include nucleic acid molecules, polypeptides, chemical structures, and cells. Methods include in vitro and in vivo processes, and the in vitro methods include chemical reactions.
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Paragraph 0193
(2016/08/23)
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- Scale-up of a chemo-biocatalytic route to (2 R,4 R)- and (2 S,4 S)-monatin
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Monatin, a natural sweetener, refers to a collection of four isomers of 2-((1H-indol-3-yl)methyl)-4-amino-2-hydroxypentanedioic acid. A chemo-biocatalytic approach to kilogram quantities of enantiopure 2S,4S-monatin and 2R,4R-monatin from indole is described. Key steps in the process include a (2 + 3) cycloaddition reaction followed by nickel-catalysed reduction to construct the monatin backbone, and a highly selective enzyme resolution of the 2S,4S- and 2R,4R-monatin diastereomeric pair to afford each enantiomer in 99% ee.
- Rousseau, Amanda L.,Buddoo, Subash R.,Gordon, Gregory E. R.,Beemadu, Sharon,Kupi, B. Godfrey,Lepuru, M. Jerry,Maumela, Munaka C.,Parsoo, Arvesh,Sibiya, Duncan M.,Brady, Dean
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p. 249 - 257
(2011/10/02)
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- Methods and systems for increasing production of equilibrium reactions
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Methods and systems for increasing the production of monatin in a multi-step equilibrium pathway are described. In some embodiments, a method includes adding alanine to a reactor along with one or more reactants and one or more enzymes, and producing a mixture comprising monatin and one or more intermediates. The addition of alanine results in a decreased concentration of less stable intermediates and an increased concentration of monatin.
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Page/Page column 19-21
(2010/06/20)
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- PRODUCTION OF MONATIN ENANTIOMERS
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Methods for the preparation of the high intensity sweetener, monatin, 3-(1-amino-1,3-dicarboxy-3-hydroxy-but-4-yl)indole, its salts and internal condensation products thereof, including methods applicable to the large-scale production of monatin are described.
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Page/Page column 11-12; sheet 1; 7
(2009/04/24)
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- PRODUCTION OF MONATIN STEREOISOMERS
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Methods and materials for the production of the high intensity sweetener, monatin, in stereoisomerically-pure or stereoisomerically-enriched form are disclosed. For example, methods using stereoisoselective hydrolysis and separation of a monatin-derived lactone ester are disclosed.
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Page/Page column 17
(2009/05/29)
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- Methods And Systems For Increasing Production of Equilibrium Reactions
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Methods and systems for increasing the production of equilibrium reactions are described. In some embodiments, a method comprises removing enzymes from a reaction mixture once equilibrium is achieved, selectively re-adding enzymes and reactants for driving the product-forming reaction to product, and optionally recycling stabilized intermediates, by-products and/or co-products back into the reaction mixture. In some embodiments, a method comprises purifying the desired product from a reaction mixture and selectively recycling one or more components of the reaction mixture, such as original reactants, intermediates, co-products or by-products back into the reaction mixture as desired to improve titer. Systems for implementing the methods are also provided. In some embodiments the methods and systems are implemented for increasing the production of monatin and monatin derivatives, produced in multi-step equilibrium pathways.
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Page/Page column 26
(2008/06/13)
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- PROCESS FOR PRODUCING MONATIN OR SALT THEREOF
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[Problems] To provide a process for producing monatin where steric configuration of 2-position is in an R configuration or a salt thereof by isomerization of 2-position of monatin where steric configuration of 2-position is in an S configuration. [Means for Resolution] A process for producing monatin where steric configuration of 2-position is in an R configuration or a salt thereof, characterized in that, the process contains a step where isomerization reaction of 2-position of monatin in which steric configuration of 2-position is in an S configuration is carried out in a mixed solvent of water and organic solvent in the presence of an aldehyde and, after that, a step where monatin in which steric configuration of 2-position is in an R configuration or a salt is crystallized.
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Page/Page column 7
(2008/06/13)
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- Process of producing glutamate derivatives
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The present invention relates to a process for producing efficiently glutamic acid derivatives (including salts thereof) such as monatin by converting a substituted α-keto acid of formula (1) into a glutamic acid derivative of formula (2) in the presence of an enzyme catalyzing conversion of the same
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Page/Page column 51
(2008/06/13)
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- PROCESS FOR PRODUCING MONATIN
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By simultaneously carrying out an isomerization reaction at position 2 of monatin in different configurations at positions 2 and 4 in the presence of an aldehyde under a condition of pH 4 to 11 in a mixture solvent of water and an organic solvent, and the crystallization of monatin in the same configurations at positions 2 and 4 or a salt thereof, monatin useful as a sweetener, particularly optically active monatin can efficiently be produced.
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Page/Page column 10
(2010/11/24)
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- Stereoselective syntheses of 4-hydroxy 4-substituted glutamic acids
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The 4-hydroxy 4-substituted glutamic acid moiety is a common substructure of biologically important natural products such as monatin [(2S,4S)-2], lycoperdic acid (3), and dysiherbaine (4). To develop methodology for syntheses of these natural products, cycloadditions of nitrone 5 with 2-substituted 2-propen-1-ols 6 and 2-substituted acrylates 8 were investigated. Reactions of nitrone 5 with alcohols 6 in the presence of MgBr2OEt2 gave cycloadducts 7 in a highly stereoselective manner, whereas noncatalyzed reactions of 5 with acrylates 8 afforded adducts 9. Using the former reaction, syntheses of monatin [(2S,4S)-2], monatin derivative 18, and lycoperdic acid (3) were accomplished. The C4-epimer of monatin [(2S,4R)-2)] was also synthesized by employing the latter cycloaddition.
- Tamura, Osamu,Shiro, Tomoya,Ogasawara, Mizuho,Toyao, Atsushi,Ishibashi, Hiroyuki
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p. 4569 - 4577
(2007/10/03)
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- Highly stereoselective synthesis of (-)-monatin, a high-intensity sweetener, using chelation-controlled nitrone cycloaddition
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Synthesis of (-)-monatin was achieved by chelation-controlled cycloaddition of nitrone 2 with allyl alcohol 3a in the presence of MgBr 2·OEt2.
- Tamura, Osamu,Shiro, Tomoya,Toyao, Atsushi,Ishibashi, Hiroyuki
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p. 2678 - 2679
(2007/10/03)
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