-
Nihon Rinsho. Japanese Journal of... Feb 1997
Review
Topics: Alcohol Dehydrogenase; Amino Acid Sequence; Animals; Base Sequence; Humans; Isoenzymes; Liver; Molecular Sequence Data; Promoter Regions, Genetic; Transcription Factors
PubMed: 9078704
DOI: No ID Found -
Impact and relevance of alcohol dehydrogenase enantioselectivities on biotechnological applications.Applied Microbiology and Biotechnology Apr 2020Alcohol dehydrogenases (ADHs) catalyze the reversible reduction of a carbonyl group to its corresponding alcohol. ADHs are widely employed for organic synthesis due to... (Review)
Review
Alcohol dehydrogenases (ADHs) catalyze the reversible reduction of a carbonyl group to its corresponding alcohol. ADHs are widely employed for organic synthesis due to their lack of harm to the environment, broad substrate acceptance, and high enantioselectivity. This review focuses on the impact and relevance of ADH enantioselectivities on their biotechnological application. Stereoselective ADHs are beneficial to reduce challenging ketones such as ketones owning two bulky substituents or similar-sized substituents to the carbonyl carbon. Meanwhile, in cascade reactions, non-stereoselective ADHs can be utilized for the quantitative oxidation of racemic alcohol to ketone and dynamic kinetic resolution.
Topics: Alcohol Dehydrogenase; Alcohols; Biotechnology; Catalysis; Ketones; Kinetics; Oxidation-Reduction; Protein Engineering; Stereoisomerism; Substrate Specificity
PubMed: 32060695
DOI: 10.1007/s00253-020-10440-2 -
Postepy Higieny I Medycyny... 1996The paper presents the new aspects of structure and kinetics of alcohol dehydrogenase. The differences in substrate specificity of isoenzymes are broadly discussed. The... (Review)
Review
The paper presents the new aspects of structure and kinetics of alcohol dehydrogenase. The differences in substrate specificity of isoenzymes are broadly discussed. The newly discovered gastric alcohol dehydrogenase is also mentioned.
Topics: Alcohol Dehydrogenase; Humans; Isoenzymes; Kinetics; Substrate Specificity
PubMed: 8778717
DOI: No ID Found -
EXS 1994Alcohol dehydrogenases constitute a complex system of enzymes, classes, isozymes, and allelic variants. The zinc containing, well-known liver enzyme is a class I... (Comparative Study)
Comparative Study Review
Alcohol dehydrogenases constitute a complex system of enzymes, classes, isozymes, and allelic variants. The zinc containing, well-known liver enzyme is a class I medium-chain alcohol dehydrogenase. Other classes of this family include the class II protein, the glutathione-dependent formaldehyde dehydrogenase (the class III enzyme), the stomach-expressed class IV form, and the recently defined class V protein. Characterized forms suggest that the glutathione-dependent formaldehyde dehydrogenase is the original ancestor, defining a role for the whole protein family in cellular defense mechanisms. The isozyme-multiple class I protein is derived from an early gene duplication, allowing sub-specialization in vertebrates. Class IV is the one most ethanol-active and appears to be derived from the class I line. Allelic variants within class I, in association with aldehyde dehydrogenase variants, correlate with population differences in ethanol metabolism and hence with susceptibility to develop alcohol-related diseases. The structures also correlate with functional properties and define molecular building units for the whole family.
Topics: Alcohol Dehydrogenase; Alcohol Drinking; Alcoholism; Animals; Biological Evolution; Humans; Isoenzymes; Mammals; Multigene Family
PubMed: 8032153
DOI: 10.1007/978-3-0348-7330-7_22 -
FEMS Microbiology Reviews Oct 1995Alcohol dehydrogenase (ADH) is a key enzyme for the production of butanol, ethanol, and isopropanol by the solvent-producing clostridia. Initial studies of ADH in... (Review)
Review
Alcohol dehydrogenase (ADH) is a key enzyme for the production of butanol, ethanol, and isopropanol by the solvent-producing clostridia. Initial studies of ADH in extracts of several strains of Clostridium acetobutylicum and C. beijerinckii gave conflicting molecular properties. A more coherent picture has emerged because of the following results: (i) identification of ADHs with different coenzyme specificities in these species; (ii) discovery of structurally conserved ADHs (type 3) in three solvent-producing species; (iii) isolation of mutants with deficiencies in butanol production and restoration of butanol production with a cloned alcohol/aldehyde dehydrogenase gene; and (iv) resolution of various 'C. acetobutylicum' cultures into four species. The three ADH isozymes of C. beijerinckii NRRL B592 have high sequence similarities to ADH-1 of Clostridium sp. NCP 262 (formerly C. acetobutylicum P262) and to the ADH domain of the alcohol/aldehyde dehydrogenase of C. acetobutylicum ATCC 824/DSM 792. The NADH-dependent activity of the ADHs from C. beijerinckii NRRL B592 and the BDHs from C. acetobutylicum ATCC 824 is profoundly affected by the pH of the assay, and the relative importance of NADH and NADPH to butanol production may be misappraised when NAD(P)H-dependent activities were measured at different pH values. The primary/secondary ADH of isopropanol-producing C. beijerinckii is a type-1 enzyme and is highly conserved in Thermoanaerobacter brockii (formerly Thermoanaerobium brockii) and Entamoeba histolytica. Several solvent-forming enzymes (primary ADH, aldehyde dehydrogenase, and 3-hydroxybutyryl-CoA dehydrogenase) are very similar between C. beijerinckii and the species represented by Clostridium sp. NCP 262 and NRRL B643. The realization of such relationships will facilitate the elucidation of the roles of different ADHs because each type of ADH can now be studied in an organism most amenable to experimental manipulations.
Topics: Alcohol Dehydrogenase; Amino Acid Sequence; Clostridium; Molecular Sequence Data; Sequence Homology, Amino Acid; Solvents
PubMed: 7576768
DOI: 10.1111/j.1574-6976.1995.tb00210.x -
Nihon Rinsho. Japanese Journal of... Aug 1999
-
Biotechnology and Applied Biochemistry Apr 2023There are three prominent alcohol dehydrogenases superfamilies: short-chain, medium-chain, and iron-containing alcohol dehydrogenases (FeADHs). Many members are valuable... (Review)
Review
There are three prominent alcohol dehydrogenases superfamilies: short-chain, medium-chain, and iron-containing alcohol dehydrogenases (FeADHs). Many members are valuable catalysts for producing industrially relevant products such as active pharmaceutical intermediates, chiral synthons, biopolymers, biofuels, and secondary metabolites. However, FeADHs are the least explored enzymes among the superfamilies for commercial tenacities. They portray a conserved structure having a "tunnel-like" cofactor and substrate binding site with particular functions, despite representing high sequence diversity. Interestingly, phylogenetic analysis demarcates enzymes catalyzing distinct native substrates where closely related clades convert similar molecules. Further, homologs from various mesophilic and thermophilic microbes have been explored for designing a solvent and temperature-resistant enzyme for industrial purposes. The review explores different iron-containing alcohol dehydrogenases potential engineering of the enzymes and substrates helpful in manufacturing commercial products.
Topics: Alcohol Dehydrogenase; Phylogeny; Amino Acid Sequence; Iron; Binding Sites
PubMed: 35751426
DOI: 10.1002/bab.2376 -
Physical Chemistry Chemical Physics :... Nov 2023Alcohol dehydrogenases (ADH) are a family of enzymes that catalyse the interconversion between ketones/aldehydes and alcohols in the presence of NADPH cofactor. It is...
Alcohol dehydrogenases (ADH) are a family of enzymes that catalyse the interconversion between ketones/aldehydes and alcohols in the presence of NADPH cofactor. It is challenging to desymmetrise the substituted cyclopentane-1,3-dione by engineering an ADH, while the reaction mechanism of the metal independent ADH remains elusive. Here we measured the conversion of a model substrate 2-benzyl-2-methylcyclopentane-1,3-dione by ADH and found it predominately gave the (2,3) product. Binding mode analysis of the substrate in ADH from molecular dynamics simulations disclosed the origin of the enantioselectivity of the enzyme; the opening and closing of the loop 191-205 above the substrate are responsible for shaping the binding pocket to orientate the substrate, so as to give different stereoisomer products. Using QM/MM calculations, we elucidated the reaction mechanism of ADH. Furthermore, we demonstrated the reaction profile corresponding to the production of different stereoisomers, which is in accordance with our experimental observations. This research here will shed a light on the rational engineering of ADH to achieve stereodivergent stereoisomer products.
Topics: Alcohol Dehydrogenase; Alcohols; Aldehydes; Catalysis; Ketones; Substrate Specificity
PubMed: 37955422
DOI: 10.1039/d3cp04019d -
International Journal of Food... Jun 2008The oxidation of ethanol to acetic acid is the most characteristic process in acetic acid bacteria. Gluconacetobacter diazotrophicus is rather unique among the acetic... (Review)
Review
The oxidation of ethanol to acetic acid is the most characteristic process in acetic acid bacteria. Gluconacetobacter diazotrophicus is rather unique among the acetic acid bacteria as it carries out nitrogen fixation and is a true endophyte, originally isolated from sugar cane. Aside its peculiar life style, Ga. diazotrophicus, possesses a constitutive membrane-bound oxidase system for ethanol. The Alcohol dehydrogenase complex (ADH) of Ga. diazotrophicus was purified to homogeneity from the membrane fraction. It-exhibited two subunits with molecular masses of 71.4 kDa and 43.5 kDa. A positive peroxidase reaction confirmed the presence of cytochrome c in both subunits. Pyrroloquinoline quinone (PQQ) of ADH was identified by UV-visible light and fluorescence spectroscopy. The enzyme was purified in its full reduced state; potassium ferricyanide induced its oxidation. Ethanol or acetaldehyde restored the full reduced state. The enzyme showed an isoelectric point (pI) of 6.1 and its optimal pH was 6.0. Both ethanol and acetaldehyde were oxidized at almost the same rate, thus suggesting that the ADH complex of Ga. diazotrophicus could be kinetically competent to catalyze, at least in vitro, the double oxidation of ethanol to acetic acid.
Topics: Acetic Acid; Alcohol Dehydrogenase; Ethanol; Food Microbiology; Gluconacetobacter; Hydrogen-Ion Concentration; Isoelectric Point; Molecular Weight; Nitrogen; Nitrogen Fixation; Oxidation-Reduction; PQQ Cofactor
PubMed: 18321602
DOI: 10.1016/j.ijfoodmicro.2007.10.015 -
Biochemistry Mar 2021Structures of yeast alcohol dehydrogenase determined by X-ray crystallography show that the subunits have two different conformational states in each of the two dimers...
Structures of yeast alcohol dehydrogenase determined by X-ray crystallography show that the subunits have two different conformational states in each of the two dimers that form the tetramer. Apoenzyme and holoenzyme complexes relevant to the catalytic mechanism were described, but the asymmetry led to questions about the cooperativity of the subunits in catalysis. This study used cryo-electron microscopy (cryo-EM) to provide structures for the apoenzyme, two different binary complexes with NADH, and a ternary complex with NAD and 2,2,2-trifluoroethanol. All four subunits in each of these complexes are identical, as the tetramers have 2 symmetry, suggesting that there is no preexisting asymmetry and that the subunits can be independently active. The apoenzyme and one enzyme-NADH complex have "open" conformations and the inverted coordination of the catalytic zinc with Cys-43, His-66, Glu-67, and Cys-153, whereas another enzyme-NADH complex and the ternary complex have closed conformations with the classical coordination of the zinc with Cys-43, His-66, Cys-153, and a water or the oxygen of trifluoroethanol. The conformational change involves interactions of Arg-340 with the pyrophosphate group of the coenzyme and Glu-67. The cryo-EM and X-ray crystallography studies provide structures relevant for the catalytic mechanism.
Topics: Alcohol Dehydrogenase; Binding Sites; Catalysis; Cryoelectron Microscopy; Crystallography, X-Ray; Models, Molecular; Oxidation-Reduction; Protein Binding; Protein Conformation; Saccharomyces cerevisiae; Substrate Specificity
PubMed: 33620215
DOI: 10.1021/acs.biochem.0c00921