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Cellular & Molecular Immunology Aug 2020Immunometabolism plays a fundamental role in health and diseases and involves multiple genes and signals. Aconitate decarboxylase 1 (ACOD1; also known as IRG1) is... (Review)
Review
Immunometabolism plays a fundamental role in health and diseases and involves multiple genes and signals. Aconitate decarboxylase 1 (ACOD1; also known as IRG1) is emerging as a regulator of immunometabolism in inflammation and infection. Upregulation of ACOD1 expression occurs in activated immune cells (e.g., macrophages and monocytes) in response to pathogen infection (e.g., bacteria and viruses), pathogen-associated molecular pattern molecules (e.g., LPS), cytokines (e.g., TNF and IFNs), and damage-associated molecular patterns (e.g., monosodium urate). Mechanistically, several immune receptors (e.g., TLRs and IFNAR), adapter proteins (e.g., MYD88), ubiquitin ligases (e.g., A20), and transcription factors (e.g., NF-κB, IRFs, and STATs) form complex signal transduction networks to control ACOD1 expression in a context-dependent manner. Functionally, ACOD1 mediates itaconate production, oxidative stress, and antigen processing and plays dual roles in immunity and diseases. On the one hand, activation of the ACOD1 pathway may limit pathogen infection and promote embryo implantation. On the other hand, abnormal ACOD1 expression can lead to tumor progression, neurodegenerative disease, and immune paralysis. Further understanding of the function and regulation of ACOD1 is important for the application of ACOD1-based therapeutic strategies in disease.
Topics: Animals; Antigen Presentation; Carboxy-Lyases; Disease; Humans; Immune System; Immunity; Oxidative Stress
PubMed: 32601305
DOI: 10.1038/s41423-020-0489-5 -
The FEBS Journal May 2023The UbiX/UbiD system is widespread in microbes and responsible for the reversible decarboxylation of unsaturated carboxylic acids. The UbiD enzyme catalyzes this unusual... (Review)
Review
The UbiX/UbiD system is widespread in microbes and responsible for the reversible decarboxylation of unsaturated carboxylic acids. The UbiD enzyme catalyzes this unusual reaction using a prenylated flavin (prFMN) as cofactor, the latter formed by the flavin prenyltransferase UbiX. A detailed picture of the biochemistry of flavin prenylation, oxidative maturation, and covalent catalysis underpinning reversible decarboxylation is emerging. This reveals the prFMN cofactor can undergo a wide range of transformations, complemented by considerable UbiD-variability. These provide a blueprint for biotechnological applications aimed at producing hydrocarbons or aromatic C-H activation through carboxylation.
Topics: Flavins; Carboxy-Lyases; Flavin Mononucleotide; Oxidation-Reduction; Dimethylallyltranstransferase
PubMed: 35073609
DOI: 10.1111/febs.16371 -
Current Opinion in Structural Biology Aug 2022The ubiquitous UbiX-UbiD system is associated with a wide range of microbial (de)carboxylation reactions. Recent X-ray crystallographic studies have contributed to... (Review)
Review
The ubiquitous UbiX-UbiD system is associated with a wide range of microbial (de)carboxylation reactions. Recent X-ray crystallographic studies have contributed to elucidating the enigmatic mechanism underpinning the conversion of α,β-unsaturated acids by this system. The UbiD component utilises a unique cofactor, prenylated flavin (prFMN), generated by the bespoke action of the associated UbiX flavin prenyltransferase. Structure determination of a range of UbiX/UbiD representatives has revealed a generic mode of action for both the flavin-to-prFMN metamorphosis and the (de)carboxylation. In contrast to the conserved UbiX, the UbiD superfamily is associated with a versatile substrate range. The latter is reflected in the considerable variety of UbiD quaternary structure, dynamic behaviour and active site architecture. Directed evolution of UbiD enzymes has taken advantage of this apparent malleability to generate new variants supporting in vivo hydrocarbon production. Other applications include coupling UbiD to carboxylic acid reductase to convert alkenes into α,β-unsaturated aldehydes via enzymatic CO fixation.
Topics: Aspergillus niger; Carboxy-Lyases; Decarboxylation; Flavins; Prenylation
PubMed: 35843126
DOI: 10.1016/j.sbi.2022.102432 -
ChemSusChem Apr 2021In recent years, (de)carboxylases that catalyze reversible (de)carboxylation have been targeted for application as carboxylation catalysts. This has led to the... (Review)
Review
In recent years, (de)carboxylases that catalyze reversible (de)carboxylation have been targeted for application as carboxylation catalysts. This has led to the development of proof-of-concept (bio)synthetic CO fixation routes for chemical production. However, further progress towards industrial application has been hampered by the thermodynamic constraint that accompanies fixing CO to organic molecules. In this Review, biocatalytic carboxylation methods are discussed with emphases on the diverse strategies devised to alleviate the inherent thermodynamic constraints and their application in synthetic CO -fixation cascades.
Topics: Biocatalysis; Biotin; Carbon Dioxide; Carboxy-Lyases; Dinitrocresols; Metals; Molecular Structure; Pyridoxal; Structure-Activity Relationship; Thermodynamics; Thiamine Pyrophosphate
PubMed: 33631048
DOI: 10.1002/cssc.202100159 -
Biochimica Et Biophysica Acta May 2001The review is concerned with three Na(+)-dependent biotin-containing decarboxylases, which catalyse the substitution of CO(2) by H(+) with retention of configuration... (Review)
Review
The review is concerned with three Na(+)-dependent biotin-containing decarboxylases, which catalyse the substitution of CO(2) by H(+) with retention of configuration (DeltaG degrees '=-30 kJ/mol): oxaloacetate decarboxylase from enterobacteria, methylmalonyl-CoA decarboxylase from Veillonella parvula and Propiogenium modestum, and glutaconyl-CoA decarboxylase from Acidaminococcus fermentans. The enzymes represent complexes of four functional domains or subunits, a carboxytransferase, a mobile alanine- and proline-rich biotin carrier, a 9-11 membrane-spanning helix-containing Na(+)-dependent carboxybiotin decarboxylase and a membrane anchor. In the first catalytic step the carboxyl group of the substrate is converted to a kinetically activated carboxylate in N-carboxybiotin. After swing-over to the decarboxylase, an electrochemical Na(+) gradient is generated; the free energy of the decarboxylation is used to translocate 1-2 Na(+) from the inside to the outside, whereas the proton comes from the outside. At high [Na(+)], however, the decarboxylases appear to catalyse a mere Na(+)/Na(+) exchange. This finding has implications for the life of P. modestum in sea water, which relies on the synthesis of ATP via Delta(mu)Na(+) generated by decarboxylation. In many sequenced genomes from Bacteria and Archaea homologues of the carboxybiotin decarboxylase from A. fermentans with up to 80% sequence identity have been detected.
Topics: Bacterial Proteins; Biotin; Carboxy-Lyases; Cations, Monovalent; Decarboxylation; Energy Metabolism; Methylmalonyl-CoA Decarboxylase; Models, Chemical; Protons; Sodium
PubMed: 11248185
DOI: 10.1016/s0005-2728(00)00273-5 -
Current Opinion in Chemical Biology Dec 2018Prenylated flavin (prFMN) is a recently discovered cofactor that underpins catalysis in the ubiquitous microbial UbiDX system. UbiX acts as a flavin prenyltransferase... (Review)
Review
Prenylated flavin (prFMN) is a recently discovered cofactor that underpins catalysis in the ubiquitous microbial UbiDX system. UbiX acts as a flavin prenyltransferase while UbiD is a prFMN-dependent reversible (de)carboxylase. The extensive modification of flavin by prenylation, and the consecutive oxidation to the prFMN azomethine ylide, leads to cofactor metamorphosis. While prFMN is no longer able to perform N5-based classical flavin chemistry, it is capable of forming cycloadducts with dipolarophiles, long-lived C4a-based radical species as well as undergoing extensive light driven isomerization. An ever-expanding range of distinct prFMN forms hints at the possibility of novel prFMN driven biochemistry yet to be discovered.
Topics: Aspergillus niger; Carboxy-Lyases; Escherichia coli; Flavins; Models, Molecular; Oxidation-Reduction; Prenylation; Pseudomonas aeruginosa
PubMed: 30326424
DOI: 10.1016/j.cbpa.2018.09.024 -
The Biochemical Journal 1950
Topics: Carboxy-Lyases
PubMed: 14791319
DOI: No ID Found -
Analytical Biochemistry Jul 2020Fatty acid photodecarboxylases (FAP) are a recently discovered family of FAD-containing, light-activated enzymes, which convert fatty acids to n-alkanes/alkenes with...
Fatty acid photodecarboxylases (FAP) are a recently discovered family of FAD-containing, light-activated enzymes, which convert fatty acids to n-alkanes/alkenes with potential applications in the manufacture of fine and speciality chemicals and fuels. Poor catalytic stability of FAPs is however a major limitation. Here, we describe a methodology to purify catalytically stable and homogeneous samples of recombinant Chlorella variabilis NC64A FAP (CvFAP) from Escherichia coli. We demonstrate however that blue light-exposure, which is required for photodecarboxylase activity, also leads to irreversible inactivation of the enzyme, especially in the absence of palmitate substrate. Photoinactivation is attributed to formation of protein based organic radicals, which were observed by EPR spectroscopy. To suppress photoinactivation, we prepared stable and catalytically active FAP in the dark. The steady-state kinetic parameters of CvFAP (k: 0.31 ± 0.06 s and K: 98.8 ± 53.3 μM) for conversion of palmitic acid to pentadecane were determined using gas chromatography. Methods described here should now enable studies of the catalytic mechanism and exploitation of FAPs in biotechnology.
Topics: Biocatalysis; Carboxy-Lyases; Escherichia coli; Fatty Acids; Free Radicals; Kinetics; Photochemical Processes
PubMed: 32348726
DOI: 10.1016/j.ab.2020.113749 -
Plant Signaling & Behavior Dec 2022The ability to biosynthesize oxalic acid can provide beneficial functions to plants; however, uncontrolled or prolonged exposure to this strong organic acid results in...
The ability to biosynthesize oxalic acid can provide beneficial functions to plants; however, uncontrolled or prolonged exposure to this strong organic acid results in multiple physiological problems. Such problems include a disruption of membrane integrity, mitochondrial function, metal chelation, and free radical formation. Recent work suggests that a CoA-dependent pathway of oxalate catabolism plays a critical role in regulating tissue oxalate concentrations in plants. Although this CoA-dependent pathway of oxalate catabolism is important, large gaps in our knowledge of the enzymes catalyzing each step remain. Evidence that an oxalyl-CoA decarboxylase (OXC) catalyzes the second step in this pathway, accelerating the conversion of oxalyl-CoA to formyl-CoA, has been reported. Induction studies revealed that OXC gene expression was upregulated in response to an exogenous oxalate supply. Phylogenetic analysis indicates that OXCs are conserved across plant species. Evolutionarily the plant OXCs can be separated into dicot and monocot classes. Multiple sequence alignments and molecular modeling suggest that OXCs have similar functionality with three conserved domains, the N-terminal PYR domain, the middle R domain, and the C-terminal PP domain. Further study of this CoA-dependent pathway of oxalate degradation would benefit efforts to develop new strategies to improve the nutrition quality of crops.
Topics: Acyl Coenzyme A; Carboxy-Lyases; Models, Molecular; Oxalates; Oxalic Acid; Phylogeny
PubMed: 35510715
DOI: 10.1080/15592324.2022.2062555 -
Applied and Environmental Microbiology Dec 2011Carboxylases are among the most important enzymes in the biosphere, because they catalyze a key reaction in the global carbon cycle: the fixation of inorganic carbon... (Review)
Review
Carboxylases are among the most important enzymes in the biosphere, because they catalyze a key reaction in the global carbon cycle: the fixation of inorganic carbon (CO₂). This minireview discusses the physiological roles of carboxylases in different microbial pathways that range from autotrophy, carbon assimilation, and anaplerosis to biosynthetic and redox-balancing functions. In addition, the current and possible future uses of carboxylation reactions in synthetic biology are discussed. Such uses include the possible transformation of the greenhouse gas carbon dioxide into value-added compounds and the production of novel antibiotics.
Topics: Bacteria; Carbon Dioxide; Carbon-Carbon Ligases; Carboxy-Lyases; Metabolic Engineering; Metabolic Networks and Pathways
PubMed: 22003013
DOI: 10.1128/AEM.05702-11