scholarly journals One-Pot Biocatalytic Preparation of Enantiopure Unusual α-Amino Acids from α-Hydroxy Acids via a Hydrogen-Borrowing Dual-Enzyme Cascade

Catalysts ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1470
Author(s):  
Fei Liu ◽  
Junping Zhou ◽  
Meijuan Xu ◽  
Taowei Yang ◽  
Minglong Shao ◽  
...  
Keyword(s):  
Amino Acids ◽  
Mandelic Acid ◽  
Catalytic Efficiency ◽  
Lactobacillus Brevis ◽  
Building Blocks ◽  
Hydroxy Acids ◽  
One Pot ◽  
Diverse Range ◽  
Enzyme Cascade ◽  
Keto Acids

Unusual α-amino acids (UAAs) are important fundamental building blocks and play a key role in medicinal chemistry. Here, we constructed a hydrogen-borrowing dual-enzyme cascade for efficient synthesis of UAAs from α-hydroxy acids (α-HAs). D-mandelate dehydrogenase from Lactobacillus brevis (LbMDH) was screened for the catalysis of α-HAs to α-keto acids but with low activity towards aliphatic α-HAs. Therefore, we rational engineered LbMDH to improve its activity towards aliphatic α-HAs. The substitution of residue Leu243 located in the substrate entrance channel with nonpolar amino acids like Met, Trp, and Ile significantly influenced the enzyme activity towards different α-HAs. Compared with wild type (WT), variant L243W showed 103 U/mg activity towards D-α-hydroxybutyric acid, 1.7 times of the WT’s 60.2 U/mg, while its activity towards D-mandelic acid decreased. Variant L243M showed 2.3 times activity towards D-mandelic acid compared to WT, and its half-life at 40 °C increased to 150.2 h comparing with 98.5 h of WT. By combining LbMDH with L-leucine dehydrogenase from Bacillus cereus, the synthesis of structurally diverse range of UAAs from α-HAs was constructed. We achieved 90.7% conversion for L-phenylglycine production and 66.7% conversion for L-α-aminobutyric acid production. This redox self-sufficient cascade provided high catalytic efficiency and generated pure products.

Biodegradable Polymers Derived from Amino Acids for Biological Applications

2010 ◽  
Vol 76 ◽  
pp. 30-35 ◽  
Author(s):  
Naomi Cohen-Arazi ◽  
Ilanit Hagag ◽  
Michal Kolitz ◽  
Abraham J. Domb ◽  
Jeoshua Katzhendler
Keyword(s):  
Amino Acids ◽  
Molecular Weight ◽  
Ring Opening ◽  
Building Blocks ◽  
Ring Opening Polymerization ◽  
Microwave Assisted Synthesis ◽  
Hydroxy Acids ◽  
Natural Amino Acids ◽  
Direct Condensation ◽  
Positively Charged

Optically active α-hydroxy acids derived from amino acids have been synthesized and polymerized into new biodegradable polyesters. The variety of functional side chains enables the design of positively charged, negatively charged, hydrophobic and hydrophilic chiral building blocks or any combination of these constituents. Hydroxy acids of 15 natural amino acids were prepared with retention of configuration using a straightforward and reliable method of diazotization of α-amino acids. Polyesters were synthesized from these hydroxy acids by a number of methods: direct condensation in bulk, microwave assisted synthesis and ring opening polymerization. The molecular weight of the prepared polymers ranges between 2000 to 5000Da for the direct condensation and the microwave methods, whereas the ring opening polymerization results in high molecular weight polymers (20000 to 30000Da). The polymers were analyzed for their optical activity (Circular Dichroism Spectroscopy), thermal properties (DSC), solubility, molecular weight and polydispersity (GPC), and aqueous degradation. These polymers were tested for their compatibility to neuronal cells growth and differentiation.

scholarly journals Computational-Designed Enzyme for β-Tyrosine Production in Lignin Valorization

Catalysts ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1310
Author(s):  
Fei Peng ◽  
Habibu Aliyu ◽  
André Delavault ◽  
Ulrike Engel ◽  
Jens Rudat
Keyword(s):  
Amino Acids ◽  
Value Chain ◽  
Aromatic Amino Acids ◽  
Catalytic Efficiency ◽  
Building Blocks ◽  
Binding Pocket ◽  
Synthesis Process ◽  
Taxus Chinensis ◽  
Lignin Valorization ◽  
Computational Enzyme Design

Lignin is an underutilized sustainable source of aromatic compounds. To valorize the low-value lignin monomers, we proposed an efficient strategy, involving enzymatic conversion from trans-p-hydroxycinnamic acids to generate valued-added canonical and non-canonical aromatic amino acids. Among them, β-amino acids are recognized as building blocks for bioactive natural products and pharmaceutical ingredients due to their attractive antitumor properties. Using computational enzyme design, the (R)-β-selective phenylalanine aminomutase from Taxus chinensis (TchPAM) was successfully mutated to accept β-tyrosine as the substrate, as well as to generate the (R)-β-tyrosine with excellent enantiopurity (ee > 99%) as the unique product from trans-p-hydroxycinnamic acid. Moreover, the kinetic parameters were determined for the reaction of four Y424 enzyme variants with the synthesis of different phenylalanine and tyrosine enantiomers. In the ammonia elimination reaction of (R)-β-tyrosine, the variants Y424N and Y424C displayed a two-fold increased catalytic efficiency of the wild type. In this work, a binding pocket in the active site, including Y424, K427, I431, and E455, was examined for its influence on the β-enantioselectivity of this enzyme family. Combining the upstream lignin depolymerization and downstream production, a sustainable value chain based on lignin is enabled. In summary, we report a β-tyrosine synthesis process from a monolignol component, offering a new way for lignin valorization by biocatalyst modification.

One-pot gram-scale synthesis of γ-hydroxybutenolides through catalyst-free annulation of α-amino acids with α-keto acids in water

2017 ◽  
Vol 58 (11) ◽  
pp. 1034-1036 ◽  
Author(s):  
Zhiqing He ◽  
Fang Fang ◽  
Jianguang Lv ◽  
Jianmin Zhang
Keyword(s):  
Amino Acids ◽  
One Pot ◽  
Catalyst Free ◽  
Keto Acids

Artificial Biocatalytic Linear Cascades to Access Hydroxy Acids, Lactones, and α- and β-Amino Acids

Catalysts ◽  
2018 ◽  
Vol 8 (5) ◽  
pp. 205 ◽  
Author(s):  
Joerg Schrittwieser ◽  
Stefan Velikogne ◽  
Wolfgang Kroutil
Keyword(s):  
Amino Acids ◽  
Building Blocks ◽  
Starting Material ◽  
Hydroxy Acids ◽  
Alternative Substrates ◽  
Target Molecules

α-, β-, and ω-Hydroxy acids, amino acids, and lactones represent common building blocks and intermediates for various target molecules. This review summarizes artificial cascades published during the last 10 years leading to these products. Renewables as well as compounds originating from fossil resources have been employed as starting material. The review provides an inspiration for new cascade designs and may be the basis to design variations of these cascades starting either from alternative substrates or extending them to even more sophisticated products.

scholarly journals Transamination-Like Reaction Catalyzed by Leucine Dehydrogenase for Efficient Co-Synthesis of α-Amino Acids and α-Keto Acids

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7287
Author(s):  
Xiaoqing Mu ◽  
Xian Feng ◽  
Tao Wu ◽  
Feng Zhou ◽  
Yao Nie ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Building Blocks ◽  
Regeneration System ◽  
Kinetics Parameters ◽  
Leucine Dehydrogenase ◽  
Keto Acids ◽  
Pharmaceutical Industries ◽  
Total Turnover ◽  
Acid Substrate

α-Amino acids and α-keto acids are versatile building blocks for the synthesis of several commercially valuable products in the food, agricultural, and pharmaceutical industries. In this study, a novel transamination-like reaction catalyzed by leucine dehydrogenase was successfully constructed for the efficient enzymatic co-synthesis of α-amino acids and α-keto acids. In this reaction mode, the α-keto acid substrate was reduced and the α-amino acid substrate was oxidized simultaneously by the enzyme, without the need for an additional coenzyme regeneration system. The thermodynamically unfavorable oxidation reaction was driven by the reduction reaction. The efficiency of the biocatalytic reaction was evaluated using 12 different substrate combinations, and a significant variation was observed in substrate conversion, which was subsequently explained by the differences in enzyme kinetics parameters. The reaction with the selected model substrates 2-oxobutanoic acid and L-leucine reached 90.3% conversion with a high total turnover number of 9.0 × 106 under the optimal reaction conditions. Furthermore, complete conversion was achieved by adjusting the ratio of addition of the two substrates. The constructed reaction mode can be applied to other amino acid dehydrogenases in future studies to synthesize a wider range of valuable products.

scholarly journals Visible-light-driven amino acids production from biomass-based feedstocks over ultrathin CdS nanosheets

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Song Song ◽  
Jiafu Qu ◽  
Peijie Han ◽  
Max J. Hülsey ◽  
Guping Zhang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Visible Light ◽  
Side Reaction ◽  
Acid Synthesis ◽  
One Pot ◽  
Amino Acid Synthesis ◽  
Preferential Formation ◽  
Keto Acids ◽  
Visible Light Driven ◽  
Order Of Magnitude

Abstract Chemical synthesis of amino acids from renewable sources is an alternative route to the current processes based on fermentation. Here, we report visible-light-driven amination of biomass-derived α-hydroxyl acids and glucose into amino acids using NH3 at 50 °C. Ultrathin CdS nanosheets are identified as an efficient and stable catalyst, exhibiting an order of magnitude higher activity towards alanine production from lactic acid compared to commercial CdS as well as CdS nanoobjects bearing other morphologies. Its unique catalytic property is attributed mainly to the preferential formation of oxygen-centered radicals to promote α-hydroxyl acids conversion to α-keto acids, and partially to the poor H2 evolution which is an undesired side reaction. Encouragingly, a number of amino acids are prepared using the current protocol, and one-pot photocatalytic conversion of glucose to alanine is also achieved. This work offers an effective catalytic system for amino acid synthesis from biomass feedstocks under mild conditions.

scholarly journals Integrated Synthesis of Nucleotide and Nucleosides Directed by Amino Acids

2018 ◽  
Author(s):  
Irene Suárez-Marina ◽  
Rebecca Turk-MacLeod ◽  
Yousef M. Abul-Haija ◽  
Piotr S. Gromski ◽  
Geoffrey Cooper ◽  
...  
Keyword(s):  
Amino Acids ◽  
Prebiotic Chemistry ◽  
Building Blocks ◽  
Reaction Networks ◽  
One Pot ◽  
Simultaneous Formation ◽  
Chemical Systems ◽  
Mild Conditions ◽  
Glycosidic Bonds ◽  
Selection Of

<p><b>Research on the origin of nucleic acids and proteins has been approached by either multi-step synthesis or simple one-pot reactions, but exploration of their prebiotic chemistry is normally done separately. However, if nucleotides and amino acids co-existed on early Earth, their mutual interactions and reactivity should be considered in exploring the emergence of complex chemical systems that can ultimately evolve. To explore this idea, we set out to investigate nucleotide/nucleoside formation by a simple dehydration reaction of the constituent building blocks (sugar, phosphate, and nucleobase) in the presence of amino acids (<i>i.e.</i> glycine,</b> <b>arginine, glutamic acid, threonine, methionine, phenylalanine and tryptophan). Herein, we report the first example of simultaneous formation of glycosidic bonds between ribose, purines, and pyrimidines under mild conditions without a catalyst or activated reagents, as well as nucleobase exchange. We observed not only the simultaneous formation of nucleotide and nucleoside isomers from several nucleobases, but also the selection of distribution of glycosylation products when glycine was present. This work shows how reaction networks of nucleotides and amino acids should be considered when exploring the emergence of catalytic networks in the context of molecular evolution. </b></p>

scholarly journals Enhanced catalytic efficiency and universality of L-amino acid deaminase achieved by a shorter proton transfer distance

2021 ◽  
Author(s):  
Yaoyun Wu ◽  
Sheng Zhang ◽  
Wei Song ◽  
Jia Liu ◽  
Xiulai Chen ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Catalytic Mechanism ◽  
Aromatic Amino Acids ◽  
Catalytic Efficiency ◽  
Charged Amino Acids ◽  
Keto Acids ◽  
Key Factor ◽  
Limiting Efficiency ◽  
Sulfur Containing

L-amino acid deaminase (LAAD, EC 1.4.3.2) catalyzes the deamination of α-amino acids. At present, sustainable enzymatic α-keto acids synthesis remains limited by the low catalytic efficiency of wild-type LAADs. In this study, catalytic mechanism was elucidated, and catalytic distance D1 between the substrate αC-H and the cofactor FAD N(5) was identified as the key factor limiting efficiency of Proteus mirabilis PmiLAAD. Shortening the distance via protein engineering improved catalytic efficiency toward six selected amino acids. The two variants with the best catalytic properties were W1, which exhibited a preference for short-chain aliphatic amino acids and charged amino acids, and W2, which showed a preference for large aromatic amino acids and sulfur-containing amino acids. The mutated residues in the two variants altered the binding pose of the substrate, α-hydrogen was improved to be more perpendicular against the plain of the isoalloxazine ring causing the angle between the substrates’ αC-H, FAD N(5), and FAD N(10) to approach 90°, and thus shortened the distance. Finally, W1 and W2 were cascade in one Escherichia coli cell to obtain strain S3, which exhibited conversion >90% and yield >100 g/L toward all selected substrates. These results provide the basis for improving industrial production of α-keto acids via microbial deamination of α-amino acids.

scholarly journals Integrated Synthesis of Nucleotide and Nucleosides Directed by Amino Acids

2018 ◽  
Author(s):  
Irene Suárez-Marina ◽  
Rebecca Turk-MacLeod ◽  
Yousef M. Abul-Haija ◽  
Piotr S. Gromski ◽  
Geoffrey Cooper ◽  
...  
Keyword(s):  
Amino Acids ◽  
Prebiotic Chemistry ◽  
Building Blocks ◽  
Reaction Networks ◽  
One Pot ◽  
Simultaneous Formation ◽  
Chemical Systems ◽  
Mild Conditions ◽  
Glycosidic Bonds ◽  
Selection Of

<p><b>Research on the origin of nucleic acids and proteins has been approached by either multi-step synthesis or simple one-pot reactions, but exploration of their prebiotic chemistry is normally done separately. However, if nucleotides and amino acids co-existed on early Earth, their mutual interactions and reactivity should be considered in exploring the emergence of complex chemical systems that can ultimately evolve. To explore this idea, we set out to investigate nucleotide/nucleoside formation by a simple dehydration reaction of the constituent building blocks (sugar, phosphate, and nucleobase) in the presence of amino acids (<i>i.e.</i> glycine,</b> <b>arginine, glutamic acid, threonine, methionine, phenylalanine and tryptophan). Herein, we report the first example of simultaneous formation of glycosidic bonds between ribose, purines, and pyrimidines under mild conditions without a catalyst or activated reagents, as well as nucleobase exchange. We observed not only the simultaneous formation of nucleotide and nucleoside isomers from several nucleobases, but also the selection of distribution of glycosylation products when glycine was present. This work shows how reaction networks of nucleotides and amino acids should be considered when exploring the emergence of catalytic networks in the context of molecular evolution. </b></p>

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