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The Journal of Biological Chemistry Oct 2014The role of evolutionary pressure on the chemical step catalyzed by enzymes is somewhat enigmatic, in part because chemistry is not rate-limiting for many optimized... (Review)
Review
The role of evolutionary pressure on the chemical step catalyzed by enzymes is somewhat enigmatic, in part because chemistry is not rate-limiting for many optimized systems. Herein, we present studies that examine various aspects of the evolutionary relationship between protein dynamics and the chemical step in two paradigmatic enzyme families, dihydrofolate reductases and alcohol dehydrogenases. Molecular details of both convergent and divergent evolution are beginning to emerge. The findings suggest that protein dynamics across an entire enzyme can play a role in adaptation to differing physiological conditions. The growing tool kit of kinetics, kinetic isotope effects, molecular biology, biophysics, and bioinformatics provides means to link evolutionary changes in structure-dynamics function to the vibrational and conformational states of each protein.
Topics: Alcohol Dehydrogenase; Animals; Bacterial Proteins; Biocatalysis; Catalytic Domain; Evolution, Molecular; Humans; Kinetics; Models, Chemical; Tetrahydrofolate Dehydrogenase
PubMed: 25210031
DOI: 10.1074/jbc.R114.565515 -
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 -
Alcoholism, Clinical and Experimental... Dec 2018Alcohol use disorders (AUDs) are complex traits, meaning that variations in many genes contribute to the risk, as does the environment. Although the total genetic... (Review)
Review
Alcohol use disorders (AUDs) are complex traits, meaning that variations in many genes contribute to the risk, as does the environment. Although the total genetic contribution to risk is substantial, most individual variations make only very small contributions. By far the strongest contributors are functional variations in 2 genes involved in alcohol (ethanol [EtOH]) metabolism. A functional variant in alcohol dehydrogenase 1B (ADH1B) is protective in people of European and Asian descent, and a different functional variant in the same gene is protective in those of African descent. A strongly protective variant in aldehyde dehydrogenase 2 (ALDH2) is essentially only found in Asians. This highlights the need to study a wide range of populations. The likely mechanism of protection against heavy drinking and AUDs in both cases is alteration in the rate of metabolism of EtOH that at least transiently elevates acetaldehyde. Other ADH and ALDH variants, including functional variations in ADH1C, have also been implicated in affecting drinking behavior and risk for alcoholism. The pattern of linkage disequilibrium in the ADH region and the differences among populations complicate analyses, particularly of regulatory variants. This critical review focuses upon the ADH and ALDH genes as they affect AUDs.
Topics: Alcohol Dehydrogenase; Alcoholism; Aldehyde Dehydrogenase, Mitochondrial; Humans; Linkage Disequilibrium
PubMed: 30320893
DOI: 10.1111/acer.13904 -
Critical Reviews in Biotechnology May 2019Alcohol dehydrogenases are a group of oxidoreductases that specifically use NAD(P) or NAD(P)H as cofactors for electron acceptance or donation and catalyze... (Review)
Review
Alcohol dehydrogenases are a group of oxidoreductases that specifically use NAD(P) or NAD(P)H as cofactors for electron acceptance or donation and catalyze interconversion between alcohols and corresponding carbonyl compounds. In addition to their physiological roles in metabolizing alcohols and aldehydes or ketones, alcohol dehydrogenases have received considerable attention with respect to their symmetry-breaking traits in catalyzing asymmetric reactions and have Accordingly, they have become widely applied in fine chemical synthesis, particularly in the production of chiral alcohols and hydroxyl compounds that are key elements in the synthesis of active pharmaceutical ingredients (API) employed in the pharmaceutical industry. The application of structural bioinformatics to the study of functional enzymes and recent scientific breakthroughs in modern molecular biotechnology provide us with an effective alternative to gain an understanding of the molecular mechanisms involved in asymmetric bioreactions and in overcoming the limitations of enzyme availability. In this review, we discuss molecular mechanisms underlying alcohol dehydrogenase-mediated asymmetric reactions, based on protein structure-function relationships from domain structure to functional active sites. The molecular principles of the catalytic machinery involving stereochemical recognition and molecular interaction are also addressed. In addition, the diversity of enzymatic functions and properties, for example, enantioselectivity, substrate specificity, cofactor dependence, metal requirement, and stability in terms of organic solvent tolerance and thermostability, are also discussed and based on a comparative analysis of high-resolution 3 D structures of representative alcohol dehydrogenases.
Topics: Alcohol Dehydrogenase; Alcohols; Amino Acid Sequence; Biotechnology; Biotransformation; Catalysis; Computational Biology; Humans; Protein Conformation; Structure-Activity Relationship
PubMed: 30700159
DOI: 10.1080/07388551.2019.1566205 -
Applied and Environmental Microbiology Dec 2022Alkanes produced by microorganisms are expected to be an alternative to fossil fuels as an energy source. Microbial synthesis of alkanes involves the formation of fatty...
Alkanes produced by microorganisms are expected to be an alternative to fossil fuels as an energy source. Microbial synthesis of alkanes involves the formation of fatty aldehydes via fatty acyl coenzyme A (acyl-CoA) intermediates derived from fatty acid metabolism, followed by aldehyde decarbonylation to generate alkanes. Advancements in metabolic engineering have enabled the construction of such pathways in various microorganisms, including Escherichia coli. However, endogenous aldehyde reductases in the host microorganisms are highly active in converting fatty aldehydes to fatty alcohols, limiting the substrate pool for alkane production. To reuse the alcohol by-product, a screening of fatty alcohol-assimilating microorganisms was conducted, and a bacterial strain, sp. strain 7-4, was found to convert 1-tetradecanol to tetradecanal. From this strain, an alcohol dehydrogenase, PsADH, was purified and found to be involved in 1-tetradecanol-oxidizing reaction. Subsequent heterologous expression of the gene in E. coli was conducted, and recombinant PsADH was purified for a series of biochemical characterizations, including cofactors, optimal reaction conditions, and kinetic parameters. Furthermore, direct alkane production from alcohol was achieved in E. coli by coexpressing PsADH with a cyanobacterial aldehyde-deformylating oxygenase and a reducing system, including ferredoxin and ferredoxin reductase, from Nostoc punctiforme PCC73102. The alcohol-aldehyde-alkane synthetic route established in this study will provide a new approach to utilizing fatty alcohols for the production of alkane biofuel. Alcohol dehydrogenases are a group of enzymes found in many organisms. Unfortunately, studies on these enzymes mainly focus on their activities toward short-chain alcohols. In this study, we discovered an alcohol dehydrogenase, PsADH, from the bacterium sp. 7-4, which can oxidize 1-tetradecanol to tetradecanal. The medium-chain aldehyde products generated by this enzyme can serve as the substrate of aldehyde-deformylating oxygenase to produce alkanes. The enzyme found in this study can be applied to the biosynthetic pathway involving the formation of medium-chain aldehydes to produce alkanes and other valuable compounds.
Topics: Escherichia coli; Alcohol Dehydrogenase; Ferredoxins; Aldehydes; Alcohols; Alkanes; Fatty Acids; Fatty Alcohols; Oxygenases
PubMed: 36416567
DOI: 10.1128/aem.01264-22 -
Journal of Biomolecular Structure &... 2022is an economically critical necrotrophic fungus that infecting many types of plants species. Although the lifestyle adaptations and genetic foundations of several...
is an economically critical necrotrophic fungus that infecting many types of plants species. Although the lifestyle adaptations and genetic foundations of several enzymes and metabolites involved in virulence during host plant infection are well studied, the role of alcohol dehydrogenase (ADH) enzymes in these processes is poorly understood. Herein, we identified a significant up-regulation of the transcriptional levels of the gene during the tomato - strain B0510 interaction and at the early stage of infection. Substantially, we used a recent approach for replacement of gene by utilizing homologous recombination to generate knock-out mutants (Δ) and their effective complementary strains (Δ/C). A strong difference in the morphology of Δ mutants from the wild type (WT) was detected, with respect to the conidiospore, conidial germination, and formation of branches, sporulation and sclerotia. In addition, the Δ1 mutants showed significant differences in their virulence on tomato leaves relative to the WT. Moreover, the Δ mutants appeared to have higher sensitivity to oxygen limitation (hypoxia) and reactive oxygen species, and had lost their ability of alcoholic fermentation compared with the WT and complementary strains. These results provide strong evidence for the requirement of the gene for fungal development, environmental adaptation and its ability for full pathogenicity.Communicated by Ramaswamy H. Sarma.
Topics: Alcohol Dehydrogenase; Virulence; Reactive Oxygen Species; Botrytis; Fungal Proteins
PubMed: 34472419
DOI: 10.1080/07391102.2021.1971112 -
Journal of Biological Inorganic... May 2021Among the several alcohol dehydrogenases, PQQ-dependent enzymes are mainly found in the α, β, and γ-proteobacteria. These proteins are classified into three main... (Review)
Review
Among the several alcohol dehydrogenases, PQQ-dependent enzymes are mainly found in the α, β, and γ-proteobacteria. These proteins are classified into three main groups. Type I ADHs are localized in the periplasm and contain one Ca-PQQ moiety, being the methanol dehydrogenase (MDH) the most representative. In recent years, several lanthanide-dependent MDHs have been discovered exploding the understanding of the natural role of lanthanide ions. Type II ADHs are localized in the periplasm and possess one Ca-PQQ moiety and one heme c group. Finally, type III ADHs are complexes of two or three subunits localized in the cytoplasmic membrane and possess one Ca-PQQ moiety and four heme c groups, and in one of these proteins, an additional [2Fe-2S] cluster has been discovered recently. From the bioinorganic point of view, PQQ-dependent alcohol dehydrogenases have been revived recently mainly due to the discovery of the lanthanide-dependent enzymes. Here, we review the three types of PQQ-dependent ADHs with special focus on their structural features and electron transfer processes. The PQQ-Alcohol dehydrogenases are classified into three main groups. Type I and type II ADHs are located in the periplasm, while type III ADHs are in the cytoplasmic membrane. ADH-I have a Ca-PQQ or a Ln-PQQ, ADH-II a Ca-PQQ and one heme-c and ADH-III a Ca-PQQ and four hemes-c. This review focuses on their structural features and electron transfer processes.
Topics: Alcohol Dehydrogenase; Electron Transport; Heme; PQQ Cofactor
PubMed: 33606117
DOI: 10.1007/s00775-021-01852-0 -
Plant Signaling & Behavior 2019(alcohol dehydrogenase 1) was involved in plant growth and development and responded to various stresses. We published a cold-induced alcohol dehydrogenase 1 gene from...
(alcohol dehydrogenase 1) was involved in plant growth and development and responded to various stresses. We published a cold-induced alcohol dehydrogenase 1 gene from , which exists 43 unique amino acids. Here, we confirmed that overexpression of in and tobacco significantly improved cold shock tolerance through electrolyte leakage, semi-lethal temperature, phenotypic and survival analysis. These results indicate that CbADH1 is the candidate gene to improve the ability of plant freezing resistance, and it has great application value.
Topics: Acclimatization; Adaptation, Physiological; Alcohol Dehydrogenase; Arabidopsis; Brassicaceae; Cold Temperature; Gene Expression Regulation, Plant; Homozygote; Plants, Genetically Modified; Seedlings; Nicotiana
PubMed: 31056000
DOI: 10.1080/15592324.2019.1612680 -
BMJ (Clinical Research Ed.) Jul 2014
Topics: Alcohol Dehydrogenase; Alcohol Drinking; Coronary Disease; Female; Humans; Male; Polymorphism, Single Nucleotide; Stroke
PubMed: 25011451
DOI: 10.1136/bmj.g4334 -
American Journal of Medical Genetics.... Mar 2018The ADH1B (Alcohol Dehydrogenase 1B (class I), Beta Polypeptide) gene and its best-known functional alleles, Arg48His (rs1229984, ADH1B*2) and Arg370Cys (rs2066702,... (Review)
Review
The ADH1B (Alcohol Dehydrogenase 1B (class I), Beta Polypeptide) gene and its best-known functional alleles, Arg48His (rs1229984, ADH1B*2) and Arg370Cys (rs2066702, ADH1B*3), have been investigated in relation to many phenotypic traits; most frequently including alcohol metabolism and alcohol drinking behaviors, but also human evolution, liver function, cancer, and, recently, the comprehensive human phenome. To understand ADH1B functions and consequences, we provide here a bioinformatic analysis of its gene regulation and molecular functions, literature review of studies focused on this gene, and a discussion regarding future research perspectives. Certain ADH1B alleles have large effects on alcohol metabolism, and this relationship particularly encourages further investigations in relation to alcoholism and alcohol-associated cancer to understand better the mechanisms by which alcohol metabolism contributes to alcohol abuse and carcinogenesis. We also observed that ADH1B has complex mechanisms that regulate its expression across multiple human tissues, and these may be involved in cardiac and metabolic traits. Evolutionary data strongly suggest that the selection signatures at the ADH1B locus are primarily related to effects other than those on alcohol metabolism. This is also supported by the involvement of ADH1B in multiple molecular pathways and by the findings of our recent phenome-wide association study. Accordingly, future studies should also investigate other functions of ADH1B potentially relevant for the human phenome. © 2017 Wiley Periodicals, Inc.
Topics: Alcohol Dehydrogenase; Alcohol Drinking; Alcoholism; Alleles; Genotype; Humans; Neoplasms; Phenotype
PubMed: 28349588
DOI: 10.1002/ajmg.b.32523