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The Journal of Biological Chemistry Dec 1945
Topics: Transaminases
PubMed: 21006939
DOI: No ID Found -
Sheng Wu Gong Cheng Xue Bao = Chinese... Jul 2018ω-Transaminase catalyzes the asymmetric reductive amination of carbonyl compounds, and has great application prospect in the preparation of chiral amines. The... (Review)
Review
ω-Transaminase catalyzes the asymmetric reductive amination of carbonyl compounds, and has great application prospect in the preparation of chiral amines. The application in synthesis of bulky chiral amines is limited by the special structure of substrate binding region in the wild-type enzyme. Moreover, there are also some drawbacks in the stereoselectivity and stability of ω-transaminase. So far, -tωransaminase satisfying the industrial requirements is still rare. In this review, we first introduce the structure and catalytic mechanism of ω-transaminase, and then discuss the structural differences between S-selective and R-selective enzymes. Molecular modification of ω-transaminase was introduced in detail, by focusing on the structure and mechanism-based molecular modification, including substrate specificity, stereoselectivity, and stability.
Topics: Amines; Catalysis; Catalytic Domain; Enzyme Stability; Protein Engineering; Substrate Specificity; Transaminases
PubMed: 30058305
DOI: 10.13345/j.cjb.170455 -
Applied Microbiology and Biotechnology Jun 2020Transaminases (TAms) are important enzymes for the production of chiral amines for the pharmaceutical and fine chemical industries. Novel TAms for use in these... (Review)
Review
Transaminases (TAms) are important enzymes for the production of chiral amines for the pharmaceutical and fine chemical industries. Novel TAms for use in these industries have been discovered using a range of approaches, including activity-guided methods and homologous sequence searches from cultured microorganisms to searches using key motifs and metagenomic mining of environmental DNA libraries. This mini-review focuses on the methods used for TAm discovery over the past two decades, analyzing the changing trends in the field and highlighting the advantages and drawbacks of the respective approaches used. This review will also discuss the role of protein engineering in the development of novel TAms and explore possible directions for future TAm discovery for application in industrial biocatalysis. KEY POINTS: • The past two decades of TAm enzyme discovery approaches are explored. • TAm sequences are phylogenetically analyzed and compared to other discovery methods. • Benefits and drawbacks of discovery approaches for novel biocatalysts are discussed. • The role of protein engineering and future discovery directions is highlighted.
Topics: Bacteria; Biocatalysis; Industrial Microbiology; Metagenomics; Protein Engineering; Substrate Specificity; Transaminases
PubMed: 32300853
DOI: 10.1007/s00253-020-10585-0 -
Trends in Pharmacological Sciences Nov 2014Alanine-glyoxylate aminotransferase 2 (AGXT2) is a multifunctional mitochondrial aminotransferase that was first identified in 1978. The physiological importance of... (Review)
Review
Alanine-glyoxylate aminotransferase 2 (AGXT2) is a multifunctional mitochondrial aminotransferase that was first identified in 1978. The physiological importance of AGXT2 was largely overlooked for three decades because AGXT2 is less active in glyoxylate metabolism than AGXT1, the enzyme that is deficient in primary hyperoxaluria type I. Recently, several novel functions of AGXT2 have been 'rediscovered' in the setting of modern genomic and metabolomic studies. It is now apparent that AGXT2 has multiple substrates and products and that altered AGXT2 activity may contribute to the pathogenesis of cardiovascular, renal, neurological, and hematological diseases. This article reviews the biochemical properties and physiological functions of AGXT2, its unique role at the intersection of key mitochondrial pathways, and its potential as a drug target.
Topics: Animals; Humans; Transaminases
PubMed: 25294000
DOI: 10.1016/j.tips.2014.09.005 -
International Journal of Molecular... Jun 2016Kynurenine aminotransferase isozymes (KATs 1-4) are members of the pyridoxal-5'-phosphate (PLP)-dependent enzyme family, which catalyse the permanent conversion of... (Review)
Review
Kynurenine aminotransferase isozymes (KATs 1-4) are members of the pyridoxal-5'-phosphate (PLP)-dependent enzyme family, which catalyse the permanent conversion of l-kynurenine (l-KYN) to kynurenic acid (KYNA), a known neuroactive agent. As KATs are found in the mammalian brain and have key roles in the kynurenine pathway, involved in different categories of central nervous system (CNS) diseases, the KATs are prominent targets in the quest to treat neurodegenerative and cognitive impairment disorders. Recent studies suggest that inhibiting these enzymes would produce effects beneficial to patients with these conditions, as abnormally high levels of KYNA are observed. KAT-1 and KAT-3 share the highest sequence similarity of the isozymes in this family, and their active site pockets are also similar. Importantly, KAT-2 has the major role of kynurenic acid production (70%) in the human brain, and it is considered therefore that suitable inhibition of this isozyme would be most effective in managing major aspects of CNS diseases. Human KAT-2 inhibitors have been developed, but the most potent of them, chosen for further investigations, did not proceed in clinical studies due to the cross toxicity caused by their irreversible interaction with PLP, the required cofactor of the KAT isozymes, and any other PLP-dependent enzymes. As a consequence of the possibility of extensive undesirable adverse effects, it is also important to pursue KAT inhibitors that reversibly inhibit KATs and to include a strategy that seeks compounds likely to achieve substantial interaction with regions of the active site other than the PLP. The main purpose of this treatise is to review the recent developments with the inhibitors of KAT isozymes. This treatise also includes analyses of their crystallographic structures in complex with this enzyme family, which provides further insight for researchers in this and related studies.
Topics: Animals; Binding Sites; Enzyme Inhibitors; Humans; Models, Molecular; Molecular Conformation; Molecular Structure; Protein Binding; Quantitative Structure-Activity Relationship; Transaminases
PubMed: 27314340
DOI: 10.3390/ijms17060946 -
The Journal of Biological Chemistry May 1961
Topics: Transaminases
PubMed: 13734750
DOI: No ID Found -
Biochemistry. Biokhimiia Dec 2017Branched-chain amino acid aminotransferases (BCATs) catalyze reversible stereoselective transamination of branched-chain amino acids (BCAAs) L-leucine, L-isoleucine, and... (Review)
Review
Branched-chain amino acid aminotransferases (BCATs) catalyze reversible stereoselective transamination of branched-chain amino acids (BCAAs) L-leucine, L-isoleucine, and L-valine. BCATs are the key enzymes of BCAA metabolism in all organisms. The catalysis proceeds through the ping-pong mechanism with the assistance of the cofactor pyridoxal 5'-phosphate (PLP). BCATs differ from other (S)-selective transaminases (TAs) in 3D-structure and organization of the PLP-binding domain. Unlike other (S)-selective TAs, BCATs belong to the PLP fold type IV and are characterized by the proton transfer on the re-face of PLP, in contrast to the si-specificity of proton transfer in fold type I (S)-selective TAs. Moreover, BCATs are the only (S)-selective enzymes within fold type IV TAs. Dual substrate recognition in BCATs is implemented via the "lock and key" mechanism without side-chain rearrangements of the active site residues. Another feature of the active site organization in BCATs is the binding of the substrate α-COOH group on the P-side of the active site near the PLP phosphate group. Close localization of two charged groups seems to increase the effectiveness of external aldimine formation in BCAT catalysis. In this review, the structure-function features and the substrate specificity of bacterial and archaeal BCATs are analyzed. These BCATs differ from eukaryotic ones in the wide substrate specificity, optimal temperature, and reactivity toward pyruvate as the second substrate. The prospects of biotechnological application of BCATs in stereoselective synthesis are discussed.
Topics: Amino Acids, Branched-Chain; Archaea; Bacteria; Structure-Activity Relationship; Substrate Specificity; Transaminases
PubMed: 29523060
DOI: 10.1134/S0006297917130028 -
ELife Jul 2022Ammonium (NH) is essential to generate the nitrogenous building blocks of life. It gets assimilated via the canonical biosynthetic routes to glutamate and is further...
Ammonium (NH) is essential to generate the nitrogenous building blocks of life. It gets assimilated via the canonical biosynthetic routes to glutamate and is further distributed throughout metabolism via a network of transaminases. To study the flexibility of this network, we constructed an glutamate auxotrophic strain. This strain allowed us to systematically study which amino acids serve as amine sources. We found that several amino acids complemented the auxotrophy either by producing glutamate via transamination reactions or by their conversion to glutamate. In this network, we identified aspartate transaminase AspC as a major connector between many amino acids and glutamate. Additionally, we extended the transaminase network by the amino acids β-alanine, alanine, glycine, and serine as new amine sources and identified d-amino acid dehydrogenase (DadA) as an intracellular amino acid sink removing substrates from transaminase reactions. Finally, ammonium assimilation routes producing aspartate or leucine were introduced. Our study reveals the high flexibility of the cellular amination network, both in terms of transaminase promiscuity and adaptability to new connections and ammonium entry points.
Topics: Amination; Amines; Amino Acids; Ammonium Compounds; Escherichia coli; Glutamic Acid; Transaminases
PubMed: 35876664
DOI: 10.7554/eLife.77492 -
Enzyme and Microbial Technology Sep 2018The use of biocatalysis for the synthesis of high value added chemical building blocks derived from biomass is becoming an increasingly important application for future...
The use of biocatalysis for the synthesis of high value added chemical building blocks derived from biomass is becoming an increasingly important application for future sustainable technologies. The synthesis of a higher value chemical from l-arabinose, the predominant monosaccharide obtained from sugar beet pulp, is demonstrated here via a transketolase and transaminase coupled reaction. Thermostable transketolases derived from Deinococcus geothermalis and Deinococcus radiodurans catalysed the synthesis of l-gluco-heptulose from l-arabinose and β-hydroxypyruvate at elevated temperatures with high conversions. β-Hydroxypyruvate, a commercially expensive compound used in the transketolase reaction, was generated in situ from l-serine and α-ketoglutaric acid via a thermostable transaminase, also from Deinococcus geothermalis. The two steps were investigated and implemented in a one-pot system for the sustainable and efficient production of l-gluco-heptulose.
Topics: Arabinose; Bacterial Proteins; Biocatalysis; Deinococcus; Enzyme Stability; Kinetics; Molecular Structure; Monosaccharides; Pyruvates; Transaminases; Transketolase
PubMed: 29887012
DOI: 10.1016/j.enzmictec.2018.05.006 -
The Journal of Biological Chemistry Jan 1947
Topics: Amino Acids; Pyridoxine; Transaminases; Vitamin B 6 Deficiency
PubMed: 20281632
DOI: No ID Found