- Glutamate as an Efficient Amine Donor for the Synthesis of Chiral β- and γ-Amino Acids Using Transaminase
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A recyclable glutamate amine donor system employing transaminase (TA), glutamate dehydrogenase (GluDH) and mutant formate dehydrogenase (FDHm) was developed, wherein amine donor Glu was regenerated using GluDH and thereby circumvented the inhibition of TA by α-ketoglutarate. Various enantiopure β-, γ-amino acids, and amines were successfully synthesized with high conversions and excellent enantiomeric excess using this system.
- Kim, Geon-Hee,Jeon, Hyunwoo,Khobragade, Taresh P.,Patil, Mahesh D.,Sung, Sihyong,Yoon, Sanghan,Won, Yumi,Sarak, Sharad,Yun, Hyungdon
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p. 1437 - 1440
(2019/02/06)
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- Influence of the aromatic moiety in α- And β-arylalanines on their biotransformation with phenylalanine 2,3-aminomutase from: Pantoea agglomerans
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In this study enantiomer selective isomerization of various racemic α- and β-arylalanines catalysed by phenylalanine 2,3-aminomutase from Pantoea agglomerans (PaPAM) was investigated. Both α- and β-arylalanines were accepted as substrates when the aryl moiety was relatively small, like phenyl, 2-, 3-, 4-fluorophenyl or thiophen-2-yl. While 2-substituted α-phenylalanines bearing bulky electron withdrawing substituents did not react, the corresponding substituted β-aryl analogues were converted rapidly. Conversion of 3- and 4-substituted α-arylalanines happened smoothly, while conversion of the corresponding β-arylalanines was poor or non-existent. In the range of pH 7-9 there was no significant influence on the conversion of racemic α- or β-(thiophen-2-yl)alanines, whereas increasing the concentration of ammonia (ammonium carbonate from 50 to 1000 mM) inhibited the isomerization progressively and decreased the amount of the by-product (i.e. (E)-3-(thiophen-2-yl)acrylic acid was detected). In all cases, the high ee values of the products indicated excellent enantiomer selectivity and stereospecificity of the isomerization except for (S)-2-nitro-α-phenylalanine (ee 92%) from the β-isomer. Substituent effects were rationalized by computational modelling revealing that one of the main factors controlling biocatalytic activity was the energy difference between the covalent regioisomeric enzyme-substrate complexes.
- Varga, Andrea,Bánóczi, Gergely,Nagy, Botond,Bencze, László Csaba,To?a, Monica Ioana,Gellért, ákos,Irimie, Florin Dan,Rétey, János,Poppe, László,Paizs, Csaba
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p. 56412 - 56420
(2016/07/06)
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- The bacterial ammonia lyase EncP: A tunable biocatalyst for the synthesis of unnatural amino acids
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Enzymes of the class I lyase-like family catalyze the asymmetric addition of ammonia to arylacrylates, yielding high value amino acids as products. Recent examples include the use of phenylalanine ammonia lyases (PALs), either alone or as a gateway to deracemization cascades (giving (S)- or (R)-α-phenylalanine derivatives, respectively), and also eukaryotic phenylalanine aminomutases (PAMs) for the synthesis of the (R)-β-products. Herein, we present the investigation of another family member, EncP from Streptomyces maritimus, thereby expanding the biocatalytic toolbox and enabling the production of the missing (S)-β-isomer. EncP was found to convert a range of arylacrylates to a mixture of (S)-α- and (S)-β-arylalanines, with regioselectivity correlating to the strength of electron-withdrawing/-donating groups on the ring of each substrate. The low regioselectivity of the wild-type enzyme was addressed via structure-based rational design to generate three variants with altered preference for either α- or β-products. By examining various biocatalyst/substrate combinations, it was demonstrated that the amination pattern of the reaction could be tuned to achieve selectivities between 99:1 and 1:99 for β:α-product ratios as desired.
- Weise, Nicholas J.,Parmeggiani, Fabio,Ahmed, Syed T.,Turner, Nicholas J.
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supporting information
p. 12977 - 12983
(2015/10/28)
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- Enantioselective acylation of β-phenylalanine acid and its derivatives catalyzed by penicillin G acylase from alcaligenes faecalis
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This study developed a simple, efficient method for producing racemic β-phenylalanine acid (BPA) and its derivatives via the enantioselective acylation catalyzed by the penicillin G acylase from Alcaligenes faecalis (Af-PGA). When the reaction was run at 25°C and pH 10 in an aqueous medium containing phenylacetamide and BPA in a molar ratio of 2:1, 8 U/mL enzyme and 0.1 M BPA, the maximum BPA conversion efficiency at 40 min only reached 36.1%, which, however, increased to 42.9% as the pH value and the molar ratio of phenylacetamide to BPA were elevated to 11 and 3:1, respectively. Under the relatively optimum reaction conditions, the maximum conversion efficiencies of BPA derivatives all reached about 50% in a relatively short reaction time (45-90 min). The enantiomeric excess value of product (eep) and enantiomeric excess value of substrate (ees) were all above 98% and 95%, respectively. These results suggest that the method established in this study is practical, effective, and environmentally benign and may be applied to industrial production of enantiomerically pure BPA and its derivatives.
- Li, Dengchao,Ji, Lilian,Wang, Xinfeng,Wei, Dongzhi
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p. 207 - 216
(2013/04/23)
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- Asymmetric synthesis of β-fluoroaryl-β-amino acids
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The conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl) amide to a range of β-fluoroaryl-α,β-unsaturated esters gave the corresponding β-amino esters with high diastereoselectivity and in good isolated yields. Sequential treatment of the resulta
- Davies, Stephen G.,Fletcher, Ai M.,Lv, Linlu,Roberts, Paul M.,Thomson, James E.
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p. 910 - 925
(2012/09/22)
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- Development of a commercial process for (S)-β-phenylalanine (1)
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The development of a commercial manufacturing route for (S)-β-phenylalanine 8, a key pharmaceutical building block, is described. The different approaches which were investigated, based on catalytic asymmetric hydrogenation of enamide intermediates and on biocatalysis using acylase and lipase hydrolyses, are compared. The lipase resolution route was chosen for scale-up, and the final two-step process, based on readily available raw materials, is shown to be robust at full manufacturing scale
- Grayson, J. Ian,Roos, Juergen,Osswald, Steffen
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scheme or table
p. 1201 - 1206
(2011/12/16)
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- Efficient tandem biocatalytic process for the kinetic resolution of aromatic β-amino acids
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We describe a simple and efficient enzymatic tandem reaction for the preparation of enantiomerically pure β-phenylalanine and its analogues from the corresponding racemates. In this process, phenylalanine aminomutase (PAM) catalyzes the stereoselective isomerization of (R)-β-phenylalanines to (S)-a-phenylalanines, which are in situ transformed to cinnamic acids by phenylalanine ammonia lyase (PAL). Preparative scale conversions are done with a mutated PAM with enhanced catalytic activity.
- Wu, Bian,Szymanski, Wiktor,De Wildeman, Stefaan,Poelarends, Gerrit J.,Feringa, Ben L.,Janssen, Dick B.
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supporting information; experimental part
p. 1409 - 1412
(2010/08/19)
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- The first aminoacylase-catalyzed enantioselective synthesis of aromatic β-amino acids
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The first aminoacylase-catalyzed enantioselective synthesis of aromatic β-amino acids is reported. The presence of an N-chloroacetyl group as acyl group in the substrate as well as the use of porcine kidney acylase I as a suitable enzyme component are prerequisites for this resolution process whereby optically active β-amino acids are formed with high enantioselectivlties of >98% ee.
- Groeger, Harald,Trauthwein, Harald,Buchholz, Stefan,Drauz, Karlheinz,Sacherer, Christiane,Godfrin, Sylve,Werner, Helge
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p. 1977 - 1978
(2007/10/03)
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- Preparation of enantiomerically enriched aromatic β-amino acids via enzymatic resolution
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A range of enantiomerically enriched aromatic β-amino acids with high e.e. have been prepared via enzymatic resolution of ethyl ester derivatives. (C) 2000 Elsevier Science Ltd.
- Faulconbridge, Susan J.,Holt, Karen E.,Garcia Sevillano, Luis,Lock, Christopher J.,Tiffin, Peter D.,Tremayne, Neil,Winter, Stephen
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p. 2679 - 2681
(2007/10/03)
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- Biocatalytic approach to enatiomerically pure β-amino acids
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β-Aryl-β-amino acids were prepared in good chemical yield and high enantiomeric purity (> 95% ee) via penicillin acylase-catalyzed hydrolysis of the corresponding N-phenylacetyl derivatives. The (R)-enantiomers were the fast-reacting isomers in all cases studied. The biocatalytic procedure described employs a very simple set of reactions using inexpensive commercially available chemicals and enzyme, and could be easily scaled up.
- Soloshonok,Fokina,Rybakova,Shishkina,Galushko,Sorochinsky,Kukhar,Savchenko,Svedas
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p. 1601 - 1610
(2007/10/02)
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