Expanding the Substrate Specificity of <i>Thermoanaerobacter pseudoethanolicus</i> Secondary Alcohol Dehydrogenase by a Dual Site Mutation

Musa, Musa; Bsharat, Odey; Karume, Ibrahim; Vieille, Claire; Takahashi, Masateru; Hamdan, Samir M.

doi:10.1002/ejoc.201701351

Cited by 27 publications

(11 citation statements)

References 64 publications

(55 reference statements)

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“…Expanding both pockets of the active site in Ile86Ala/Trp110Ala Te SADH enabled this enzyme to accommodate ketones bearing bulky substituents on both sides, [59] which are not substrates for most known ADHs. More specifically, 1,2‐diphenylethanone was reduced with high ee and yield to produce its R alcohol (Scheme 9), which is an analog of anticancer agent combretastatin.…”

Section: Tesadh and Tbsadh Mutantsmentioning

confidence: 99%

Secondary Alcohol Dehydrogenases from Thermoanaerobacter pseudoethanolicus and Thermoanaerobacter brockii as Robust Catalysts

2021

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Alcohol dehydrogenases (ADHs) are an important type of enzyme that have significant applications as biocatalysts. Secondary ADHs from Thermoanaerobacter pseudoethanolicus (TeSADH) and Thermoanaerobacter brockii (TbSADH) are well‐known as robust catalysts. However, like most other ADHs, these enzymes suffer from their high substrate specificities (i. e., limited substrate scope), which to some extent restricts their use as biocatalysts. This minireview discusses recent efforts to expand the substrate scope and tune the enantioselectivity of TeSADH and TbSADH by using site‐directed mutagenesis and directed evolution. Various examples of asymmetric synthesis of optically active alcohols using both enzymes are highlighted. Moreover, the unique thermal stability and organic solvent tolerance of these enzymes is illustrated by their concurrent inclusion with other interesting reactions to synthesize optically active alcohols and amines. For instance, TeSADH has been used in quantitative non‐stereoselective oxidation of alcohols to deracemize alcohols via cyclic deracemization and in the racemization of enantiopure alcohols to accomplish a bienzymatic dynamic kinetic resolution.

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Section: Tesadh and Tbsadh Mutantsmentioning

confidence: 99%

Secondary Alcohol Dehydrogenases from Thermoanaerobacter pseudoethanolicus and Thermoanaerobacter brockii as Robust Catalysts

2021

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“…Asymmetric reduction of prochiral ketone via biocatalysis is one of the most promising routes to prepare optically active alcohols. [1][2][3][4][5][6] Molecules with tetralone rings are used for the synthesis of many biological active and drug precursors. For example, Sertraline with a tetralone ring is used to treat disorder such as obsessive compulsive, post-traumatic stress, premenstrual dysphoric, and social anxiety.…”

Section: Introductionmentioning

confidence: 99%

Biocatalytic asymmetric synthesis of (R)‐1‐tetralol using Lactobacillus paracasei BD101

Kalay

Şahin

2021

Chirality

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Asymmetric bioreduction of ketones is a fundamental process in the production of organic molecules. Compounds containing tetralone rings are found in the structure of many biologically active and pharmaceutical molecules. Biocatalytic reduction of ketones is one of the most promising and significant routes to prepare optically active alcohols. In this study, the reductive capacity of Lactobacillus paracasei BD101 was investigated as whole-cell biocatalyst in the enantioselective reduction of 1-tetralone (1). In biocatalytic reduction reactions, the conversion of the substrate and the enantiomeric excess (ee) of the product are significantly affected by optimization parameters such as temperature, agitation rate, pH, and incubation time. Effects of these parameters on ee and conversion were investigated comprehensively. (R)-1-tetralol ((R)-2), which can be used to treat disorder such as obsessive compulsive, posttraumatic stress, premenstrual dysphoric, and social anxiety, was manufactured in enantiopure form, high yield and gram-scale, using whole-cell biocatalysts of L. paracasei BD101. The 7.04 g of (R)-2 was obtained in optically pure form with 95% yield. Also, to our knowledge, this is the first report on production of (R)-2 using whole-cell biocatalyst in excellent yield, conversion, enantiopure form and gram scale. This is a clean, eco-friendly and cheap method for the synthesis of (R)-2 compared with chemical catalyst.

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“…Methyl transferases perform highly regioselective methylations in vivo and have also been successfully employed in biocatalysis for regioselective alkyl transfer, in some cases using non-natural derivatives of the S-adenosyl methionine (SAM) cofactor as alkyl donors [29][30][31][32][33]. Oxidoreductases are also capable of differentiating between identical functional groups: Alcohol dehydrogenases have been found to reduce one carbonyl group of diketo compounds with very high regio-and enantioselectivity [34,35], and both native and evolved P450 monooxygenases have successfully been applied in the regio-and stereoselective hydroxylation of arenes, linear alkanes, terpenes, and steroids [36][37][38][39][40][41][42][43][44][45]. Also worth mentioning is the oxidative monocleavage of dialkenes at the expense of molecular oxygen that has been achieved using an enzyme preparation from the fungus Trametes hirsuta [46].…”

Section: Introductionmentioning

confidence: 99%

Regioselective Biocatalytic Transformations Employing Transaminases and Tyrosine Phenol Lyases

2018

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Regioselective reactions allow the differentiation between two or more chemically identical reactive centers within the same molecule. They are highly desirable transformations in organic synthesis, as they avoid additional chemical operations and sophisticated protection/deprotection strategies. In this context, enzymes, which present exquisite selectivity and reactivity, have been widely employed as catalysts in numerous regioselective transformations. This review focuses on two recently developed biocatalytic processes that present outstanding regioselectity: the transaminase-catalyzed asymmetric amination of di-and triketo compounds, and the stereoselective CC coupling between phenol derivatives, ammonia and pyruvate for the synthesis of tyrosine analogues, catalyzed by tyrosine phenol lyases. Additionally, elegant and straightforward cascades that have combined the aforementioned biotransformations with other enzymatic and/or chemocatalytic processes are compiled in this contribution. Overall, this review aims to provide a general view of the synthetic possibilities that two relatively recently described regio-and stereoselective biotransformations can provide.

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Expanding the Substrate Specificity of Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase by a Dual Site Mutation

Cited by 27 publications

References 64 publications

Secondary Alcohol Dehydrogenases from Thermoanaerobacter pseudoethanolicus and Thermoanaerobacter brockii as Robust Catalysts

Secondary Alcohol Dehydrogenases from Thermoanaerobacter pseudoethanolicus and Thermoanaerobacter brockii as Robust Catalysts

Biocatalytic asymmetric synthesis of (R)‐1‐tetralol using Lactobacillus paracasei BD101

Regioselective Biocatalytic Transformations Employing Transaminases and Tyrosine Phenol Lyases

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