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Angewandte Chemie (International Ed. in... Sep 2018Alcohol dehydrogenases can act as powerful catalysts in the preparation of optically pure γ-hydroxy-δ-lactones by means of an enantioconvergent dynamic redox...
Alcohol dehydrogenases can act as powerful catalysts in the preparation of optically pure γ-hydroxy-δ-lactones by means of an enantioconvergent dynamic redox isomerization of readily available Achmatowicz-type pyranones. Imitating the traditionally metal-mediated "borrowing hydrogen" approach to shuffle hydrides across molecular architectures and interconvert functional groups, this chemoinspired and purely biocatalytic interpretation effectively expands the enzymatic toolbox and provides new opportunities in the assembly of multienzyme cascades and tailor-made cellular factories.
Topics: Alcohol Dehydrogenase; Biocatalysis; Escherichia coli; Hydrogen; Isomerism; Lactones; Oxidation-Reduction; Oxidoreductases; Recombinant Proteins; Stereoisomerism
PubMed: 29984878
DOI: 10.1002/anie.201804911 -
FEMS Microbiology Reviews Dec 2003Many studies have been undertaken to characterise alcohol dehydrogenases (ADHs) from thermophiles and hyperthermophiles, mainly to better understand their activities and... (Review)
Review
Many studies have been undertaken to characterise alcohol dehydrogenases (ADHs) from thermophiles and hyperthermophiles, mainly to better understand their activities and thermostability. To date, there are 20 thermophilic archaeal and 17 thermophilic bacterial strains known to have ADHs or similar enzymes, including the hypothetical proteins. Some of these thermophiles are found to have multiple ADHs, sometimes of different types. A rigid delineation of amino acid sequences amongst currently elucidated thermophilic ADHs and similar proteins is phylogenetically apparent. All are NAD(P)-dependent, with one exception that utilises the cofactor F(420) instead. Within the NAD(P)-dependent group, the thermophilic ADHs are orderly clustered as zinc-dependent ADHs, short-chain ADHs, and iron-containing/activated ADHs. Distance matrix calculations reveal that thermophilic ADHs within one type are homologous, with those derived from a single genus often showing high similarities. Elucidation of the enzyme activity and stability, coupled with structure analysis, provides excellent information to explain the relationship between them, and thermophilic ADHs diversity.
Topics: Alcohol Dehydrogenase; Amino Acid Sequence; Archaea; Bacteria; Molecular Sequence Data
PubMed: 14638414
DOI: 10.1016/S0168-6445(03)00068-8 -
Journal of Dairy Science Sep 2015Many human gastrointestinal facultative anaerobic and aerobic bacteria possess alcohol dehydrogenase (ADH) activity and are therefore capable of oxidizing ethanol to...
Many human gastrointestinal facultative anaerobic and aerobic bacteria possess alcohol dehydrogenase (ADH) activity and are therefore capable of oxidizing ethanol to acetaldehyde. However, the ADH activity of Lactococcus spp., except Lactococcus lactis ssp. lactis, has not been widely determined, though they play an important role as the starter for most cheesemaking technologies. Cheese is a functional food recognized as an aid to digestion. In the current study, the ADH activity of Lactococcus chungangensis CAU 28(T) and 11 reference strains from the genus Lactococcus was determined. Only 5 strains, 3 of dairy origin, L. lactis ssp. lactis KCTC 3769(T), L. lactis ssp. cremoris KCCM 40699(T), and Lactococcus raffinolactis DSM 20443(T), and 2 of nondairy origin, Lactococcus fujiensis NJ317(T) and Lactococcus chungangensis CAU 28(T) KCTC 13185(T), showed ADH activity and possessed the ADH gene. All these strains were capable of making cheese, but the highest level of ADH activity was found in L. chungangensis, with 45.9nmol/min per gram in tryptic soy broth and 65.8nmol/min per gram in cream cheese. The extent that consumption of cheese, following imbibing alcohol, reduced alcohol uptake was observed by following the level of alcohol in the serum of mice. The results show a potential novel benefit of cheese as a dairy functional food.
Topics: Alcohol Dehydrogenase; Animals; Cell Line, Tumor; Cell Survival; Cheese; Culture Media; Ethanol; Food Handling; L-Lactate Dehydrogenase; Lactococcus; Mice; Mice, Inbred ICR
PubMed: 26142864
DOI: 10.3168/jds.2015-9697 -
Molecules (Basel, Switzerland) Feb 2020Diazo compounds are versatile reagents in chemical synthesis and biology due to the tunable reactivity of the diazo functionality and its compatibility with living...
Diazo compounds are versatile reagents in chemical synthesis and biology due to the tunable reactivity of the diazo functionality and its compatibility with living systems. Much effort has been made in recent years to explore their accessibility and synthetic potential; however, their preparation through stereoselective enzymatic asymmetric synthesis has been scarcely reported in the literature. Alcohol dehydrogenases (ADHs, also called ketoreductases, KREDs) are powerful redox enzymes able to reduce carbonyl compounds in a highly stereoselective manner. Herein, we have developed the synthesis and subsequent bioreduction of nine α-diazo-β-keto esters to give optically active α-diazo-β-hydroxy esters with potential applications as chiral building blocks in chemical synthesis. Therefore, the syntheses of prochiral α-diazo-β-keto esters bearing different substitution patterns at the adjacent position of the ketone group (NCH, ClCH, BrCH, CHOCH, NCSCH, CH, and Ph) and in the alkoxy portion of the ester functionality (Me, Et, and Bn), were carried out through the diazo transfer reaction to the corresponding β-keto esters in good to excellent yields (81-96%). After performing the chemical reduction of α-diazo-β-keto esters with sodium borohydride and developing robust analytical conditions to monitor the biotransformations, their bioreductions were exhaustively studied using in-house made overexpressed and commercially available KREDs. Remarkably, the corresponding α-diazo-β-hydroxy esters were obtained in moderate to excellent conversions (60 to >99%) and high selectivities (85 to >99% ) after 24 h at 30 °C. The best biotransformations in terms of conversion and enantiomeric excess were successfully scaled up to give the expected chiral alcohols with almost the same activity and selectivity values observed in the enzyme screening experiments.
Topics: Alcohol Dehydrogenase; Bacterial Proteins; Catalysis; Escherichia coli; Esters; Rhodococcus
PubMed: 32093093
DOI: 10.3390/molecules25040931 -
Journal of Bacteriology Apr 2015Thermoanaerobacterium saccharolyticum and Clostridium thermocellum are anaerobic thermophilic bacteria being investigated for their ability to produce biofuels from...
UNLABELLED
Thermoanaerobacterium saccharolyticum and Clostridium thermocellum are anaerobic thermophilic bacteria being investigated for their ability to produce biofuels from plant biomass. The bifunctional alcohol and aldehyde dehydrogenase gene, adhE, is present in these bacteria and has been known to be important for ethanol formation in other anaerobic alcohol producers. This study explores the inactivation of the adhE gene in C. thermocellum and T. saccharolyticum. Deletion of adhE reduced ethanol production by >95% in both T. saccharolyticum and C. thermocellum, confirming that adhE is necessary for ethanol formation in both organisms. In both adhE deletion strains, fermentation products shifted from ethanol to lactate production and resulted in lower cell density and longer time to reach maximal cell density. In T. saccharolyticum, the adhE deletion strain lost >85% of alcohol dehydrogenase (ADH) activity. Aldehyde dehydrogenase (ALDH) activity did not appear to be affected, although ALDH activity was low in cell extracts. Adding ubiquinone-0 to the ALDH assay increased activity in the T. saccharolyticum parent strain but did not increase activity in the adhE deletion strain, suggesting that ALDH activity was inhibited. In C. thermocellum, the adhE deletion strain lost >90% of ALDH and ADH activity in cell extracts. The C. thermocellum adhE deletion strain contained a point mutation in the lactate dehydrogenase gene, which appears to deregulate its activation by fructose 1,6-bisphosphate, leading to constitutive activation of lactate dehydrogenase.
IMPORTANCE
Thermoanaerobacterium saccharolyticum and Clostridium thermocellum are bacteria that have been investigated for their ability to produce biofuels from plant biomass. They have been engineered to produce higher yields of ethanol, yet questions remain about the enzymes responsible for ethanol formation in these bacteria. The genomes of these bacteria encode multiple predicted aldehyde and alcohol dehydrogenases which could be responsible for alcohol formation. This study explores the inactivation of adhE, a gene encoding a bifunctional alcohol and aldehyde dehydrogenase. Deletion of adhE reduced ethanol production by >95% in both T. saccharolyticum and C. thermocellum, confirming that adhE is necessary for ethanol formation in both organisms. In strains without adhE, we note changes in biochemical activity, product formation, and growth.
Topics: Alcohol Dehydrogenase; Aldehyde Oxidoreductases; Clostridium thermocellum; Ethanol; Fermentation; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Enzymologic; Gene Knockdown Techniques; Molecular Sequence Data; Mutation; Thermoanaerobacterium
PubMed: 25666131
DOI: 10.1128/JB.02450-14 -
International Journal of Molecular... Sep 2021Alcohol is a psychoactive substance that is widely used and, unfortunately, often abused. In addition to acute effects such as intoxication, it may cause many chronic... (Review)
Review
Alcohol is a psychoactive substance that is widely used and, unfortunately, often abused. In addition to acute effects such as intoxication, it may cause many chronic pathological conditions. Some of the effects are very well described and explained, but there are still gaps in the explanation of empirically co-founded dysfunction in many alcohol-related conditions. This work focuses on reviewing actual knowledge about the toxic effects of ethanol and its degradation products.
Topics: Acetaldehyde; Alcohol Dehydrogenase; Alcohol Drinking; Alcohol-Related Disorders; Ethanol; Gene Expression Regulation, Enzymologic; Humans; Metabolic Networks and Pathways; Organ Specificity; Oxidative Stress
PubMed: 34575850
DOI: 10.3390/ijms22189686 -
Human Genomics Jan 2009Alcoholism is a complex behavioural disorder. Molecular genetics studies have identified numerous candidate genes associated with alcoholism. It is crucial to verify the... (Review)
Review
Alcoholism is a complex behavioural disorder. Molecular genetics studies have identified numerous candidate genes associated with alcoholism. It is crucial to verify the disease susceptibility genes by correlating the pinpointed allelic variations to the causal phenotypes. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the principal enzymes responsible for ethanol metabolism in humans. Both ADH and ALDH exhibit functional polymorphisms among racial populations; these polymorphisms have been shown to be the important genetic determinants in ethanol metabolism and alcoholism. Here, we briefly review recent advances in genomic studies of human ADH/ALDH families and alcoholism, with an emphasis on the pharmacogenetic consequences of venous blood acetaldehyde in the different ALDH2 genotypes following the intake of various doses of ethanol. This paper illustrates a paradigmatic example of phenotypic verifications in a protective disease gene for substance abuse.
Topics: Acetaldehyde; Alcohol Dehydrogenase; Alcoholism; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; Alleles; Ethanol; Genetic Variation; Humans; Polymorphism, Genetic
PubMed: 19164089
DOI: 10.1186/1479-7364-3-2-121 -
ChemistryOpen Apr 2022Biocatalytic production of both enantiomers of optically active alcohols with high enantiopurities is of great interest in industry. Alcohol dehydrogenases (ADHs)... (Review)
Review
Biocatalytic production of both enantiomers of optically active alcohols with high enantiopurities is of great interest in industry. Alcohol dehydrogenases (ADHs) represent an important class of enzymes that could be used as catalysts to produce optically active alcohols from their corresponding prochiral ketones. This review covers examples of the synthesis of optically active alcohols using ADHs that exhibit anti-Prelog stereopreference. Both wild-type and engineered ADHs that exhibit anti-Prelog stereopreference are highlighted.
Topics: Alcohol Dehydrogenase; Alcohols; Biocatalysis; Ketones; Stereoisomerism
PubMed: 35191611
DOI: 10.1002/open.202100251 -
ACS Applied Materials & Interfaces Jun 2020Recently, it has been shown that enzyme encapsulation inside metal-organic frameworks (MOFs) can increase enzyme activity and serve as protection from adverse...
Recently, it has been shown that enzyme encapsulation inside metal-organic frameworks (MOFs) can increase enzyme activity and serve as protection from adverse environmental conditions. Little is understood about how the enzymes move into and are held inside the MOFs although it is believed that intermolecular forces between the MOF and the enzyme cause it to be held in place. If this process can be better understood, it can have dramatic implications on the cost-effectiveness and implementation of enzyme-MOF complexes. This is of specific importance in the medical sector for protein therapy and the industrial sector where enzyme use is expected to increase. Herein, we synthesized alcohol dehydrogenase (ADH) and PCN-333 to study encapsulation, stability, and enzyme activity to expand the knowledge of our field and offer a potential improvement to a synthetic route for biofuel synthesis. From this, we found a correlation between the concentration of a buffer and the loading of an enzyme, with surprising loading trends. We conclude that the buffer solution decreases interactions between the enzyme and MOF, supporting conventional theory and allowing it to penetrate deeper into the structure causing higher enzyme loading while allowing for excellent stability over time at various pH values and temperatures and after multiple reactions. We also observe new trends such as a rebounding effect in loading and "out-of-bounds" reactions.
Topics: Alcohol Dehydrogenase; Biocatalysis; Enzyme Stability; Enzymes, Immobilized; Hydrogen-Ion Concentration; Metal-Organic Frameworks; Temperature
PubMed: 32478509
DOI: 10.1021/acsami.0c06964 -
FEBS Open Bio Feb 2019Enzymes originating from hostile environments offer exceptional stability under industrial conditions and are therefore highly in demand. Using single-cell genome data,...
Enzymes originating from hostile environments offer exceptional stability under industrial conditions and are therefore highly in demand. Using single-cell genome data, we identified the alcohol dehydrogenase (ADH) gene, , from the Atlantis II Deep Red Sea brine pool. ADH/A1a is highly active at elevated temperatures and high salt concentrations (optima at 70 °C and 4 m KCl) and withstands organic solvents. The polyextremophilic ADH/A1a exhibits a broad substrate scope including aliphatic and aromatic alcohols and is able to reduce cinnamyl-methyl-ketone and raspberry ketone in the reverse reaction, making it a possible candidate for the production of chiral compounds. Here, we report the affiliation of ADH/A1a to a rare enzyme family of microbial cinnamyl alcohol dehydrogenases and explain unique structural features for halo- and thermoadaptation.
Topics: Alcohol Dehydrogenase; Indian Ocean; Salts; Temperature
PubMed: 30761247
DOI: 10.1002/2211-5463.12557