Microbial alcohol dehydrogenases: recent developments and applications in asymmetric synthesis

Chadha, Anju; Padhi, Santosh Kumar; Stella, Selvaraj; Venkataraman, Sowmyalakshmi; Saravanan, Thangavelu

doi:10.1039/d3ob01447a

Cited by 8 publications

(4 citation statements)

References 143 publications

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“…Alcohol dehydrogenases (ADHs), belonging to the oxidoreductase class of enzymes, catalyze the production of alcohols and their oxidation to the corresponding aldehydes or ketones [1,2]. They are ubiquitous in all three domains of life and are classified into three groups based on their sizes: short-chain (group I), medium-chain (group II), and long-chain (group III) ADHs, respectively.…”

Section: Introductionmentioning

confidence: 99%

Molecular Characterization of the Iron-Containing Alcohol Dehydrogenase from the Extremely Thermophilic Bacterium Pseudothermotoga hypogea

Hao,

Ayinla,

2024

Microorganisms

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Pseudothermotoga hypogea is an extremely thermophilic bacterium capable of growing at 90 °C and producing ethanol, which is catalyzed by an alcohol dehydrogenase (ADH). The gene encoding P. hypogea ADH (PhADH) was cloned, sequenced and over-expressed. The gene sequence (1164 bp) was obtained by sequencing all fragments of the gene, which were amplified from the genomic DNA. The deduced amino acid sequence showed high identity to iron-containing ADHs from other Thermotoga species and harbored typical iron- and NADP-binding motifs, Asp195His199His268His282 and Gly39Gly40Gly41Ser42, respectively. Structural modeling showed that the N-terminal domain of PhADH contains an α/β-dinucleotide-binding motif and that its C-terminal domain is an α-helix-rich region containing the iron-binding motif. The recombinant PhADH was soluble, active, and thermostable, with a subunit size of 43 ± 1 kDa revealed by SDS-PAGE analyses. The recombinant PhADH (69 ± 2 U/mg) was shown to have similar properties to the native enzyme. The optimal pH values for alcohol oxidation and aldehyde reduction were 11.0 and 8.0, respectively. It was also thermostable, with a half-life of 5 h at 70 °C. The successful expression of the recombinant PhADH in E. coli significantly enhanced the yield of enzyme production and thus will facilitate further investigation of the catalytic mechanisms of iron-containing ADHs.

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Section: Introductionmentioning

confidence: 99%

Molecular Characterization of the Iron-Containing Alcohol Dehydrogenase from the Extremely Thermophilic Bacterium Pseudothermotoga hypogea

Hao,

Ayinla,

2024

Microorganisms

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“…Redox biocatalysis requires a cofactor to complete the redox cycle. The cofactor is reduced, or oxidised, according to the reaction type [ 22 , 37 ]. There are two types of cofactors for ADH, nicotinamide adenine dinucleotide non-phosphorylated (NADH/NAD + ) and its phosphorylated form (NADPH/NADP + ; see Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have shown that the reaction can be judiciously manipulated by altering the reaction conditions, such as varying the solvent to yield excess R or S alcohol products from corresponding ketones [ 58 , 59 ]. Along with solvent, temperature and pH, play a significant role in achieving the desired enantiomeric conversion [ 22 , 37 , [60] , [61] , [62] , [63] , [64] ].…”

Section: Introductionmentioning

confidence: 99%

Influence of deep eutectic solvents on redox biocatalysis involving alcohol dehydrogenases

Baby,

Savitha,

Kinsella

et al. 2024

Heliyon

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“…Unfortunately, such examples are scarce and mostly involve the combination of laccases with RLi compounds, [26,27] with no reported instances to date of synergistic combination between RLi reagents and enzymes for the development of multi-step stereoselective processes. Consequently, and trying to finish with this discontinuity in the design of stereoselective chemoenzymatic protocols, we decided to focus our interest in exploring the potential combination of organolithium reagents with alcohol dehydrogenases (ADHs), enzymes capable of catalyzing prochiral ketone bioreduction processes, [28][29][30][31] that have previously demonstrated high compatibility with a wide array of chemical reagents and catalysts. [32] Encouraged by previous results achieved by our research group in the stoichiometric addition of RLi to nitriles for their chemoselective and fast conversion into the corresponding prochiral ketones (working under neat conditions, at room temperature and in the absence of protecting atmosphere), [33][34][35][36][37][38][39][40] we have devised the chemoenzymatic sequence presented in Scheme 1.…”

Section: Introductionmentioning

confidence: 99%

Merging Organolithium Chemistry and Stereoselective Biocatalysis: Transformation of Aromatic Nitriles into Chiral Alcohols

Ríos‐Lombardía,

Morís‐Menéndez,

Lavandera

et al. 2024

Adv Synth Catal

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The combination of RLi‐mediated organic transformations (under air and at room temperature) with a subsequent stereoselective biocatalytic reaction is for the first time presented. Most of the previous asymmetric chemoenzymatic routes have been limited to the concomitant or sequential combination of transition metals/organocatalysts with enzymes. However, the use of polar organometallic reagents (RLi) in the design of these stereoselective hybrid protocols has been totally neglected, as far as we are concerned. Thus, in this work, the combination of organolithium chemistry and asymmetric biocatalysis is described for the first time in a one‐pot fashion. The chemoenzymatic approach converts a series of nitriles into chiral alcohols consisting of two steps, where the key item was the finding of suitable conditions to adapt the reactivities of organolithiums and alcohol dehydrogenases (ADHs) in the same recipient. The organolithium addition occurred with total chemoselectivity (no side reactions were observed) under neat conditions and room temperature leading to the corresponding imines, which were hydrolyzed using a buffer, and adjusting the pH for the subsequent ADH action. Commercial and made in house overexpressed ADHs allowed to produce chiral alcohols with excellent selectivities and good overall yields. The different behavior displayed for the reductive enzymes in the presence of diethyl ether clearly influenced in the decision to let the organolithium solvent evaporate under open‐air conditions before developing the bioreduction step. Our results demonstrate the importance of the fine orchestration of the reaction conditions for the development of efficient hybrid chemoenzymatic cascades without the need of intermediate isolation/purification steps or compartmentalization of the different synthetic systems.

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Microbial alcohol dehydrogenases: recent developments and applications in asymmetric synthesis

Abstract: In this review article, recent developments and applications of microbial alcohol dehydrogenases are summarized by emphasizing notable examples.

Cited by 8 publications

References 143 publications

Molecular Characterization of the Iron-Containing Alcohol Dehydrogenase from the Extremely Thermophilic Bacterium Pseudothermotoga hypogea

Molecular Characterization of the Iron-Containing Alcohol Dehydrogenase from the Extremely Thermophilic Bacterium Pseudothermotoga hypogea

Influence of deep eutectic solvents on redox biocatalysis involving alcohol dehydrogenases

Merging Organolithium Chemistry and Stereoselective Biocatalysis: Transformation of Aromatic Nitriles into Chiral Alcohols

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