Deracemization of Mexiletine Biocatalyzed by ω-Transaminases

Koszelewski, Dominik; Pressnitz, Desiree; Clay, Dorina; Kroutil, Wolfgang

doi:10.1021/ol901834x

Cited by 121 publications

(99 citation statements)

References 35 publications

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“…It is well known that PLP usually presents a destabilizing effect on -TAs at concentrations higher than 1 mM [25], therefore it is commonly used within 1 and 0.1 mM in enzymatic reactions and storage buffer [38,39]. As shown, the enzyme at concentrations greater than 5 mM of cofactor loses the activity significantly faster than 0.1 mM, confirming the destabilization effect (Figure 4.A).…”

Section:  Optimal Operation Ph and Temperaturesupporting

confidence: 54%

Characterization of a novel amine transaminase from Halomonas elongata

Cerioli

Planchestainer

Cassidy

et al. 2015

Journal of Molecular Catalysis B: Enzymatic

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Chiral amines are indispensable building blocks in the production of biologically active compounds. They are fundamental for the pharmaceutical industry, both as active molecules themselves and as chiral auxiliaries in asymmetric synthesis; however, the available synthetic strategies often present disadvantages. ω-Transaminases (ω-TAs) appear as an attractive alternative by driving the stereoselective amination of prochiral ketones. HEWT is a novel amine transaminase from the moderate halophilic bacterium, Halomonas elongata DSM 2581, which is highly (S)-selective, being able to fully convert (S)-1-phenylethylamine to acetophenone and showing no activity with the corresponding (R)-1-phenylethylamine. HEWT has a broad substrate scope, active with a range of amino donors and acceptors, and naturally accepts isopropylamine (IPA) as amino donor in asymmetric synthesis providing a 41% conversion of pyruvate in 24 h at 37 °C starting with 1:1 molar ratio between the reagents. HEWT also accepts ortho-xylylenediamine as amino donor in for amine synthesis, in particular, with benzaldehyde yielding high conversions between 90 and 95%. The enzyme is also tolerant to the presence of cosolvents up to 20% making it a promising candidate for industrial applications

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Section:  Optimal Operation Ph and Temperaturesupporting

confidence: 54%

Characterization of a novel amine transaminase from Halomonas elongata

Cerioli

Planchestainer

Cassidy

et al. 2015

Journal of Molecular Catalysis B: Enzymatic

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“…An important feature of this coupled enzyme system is no requirement of cofactor recycling and the irreversible equilibrium shift owing to CO 2 evaporation. In a different elegant approach, pyruvate was recycled back into alanine using an amino acid dehydrogenase and an additional dehydrogenase for the cofactor recycling (Koszelewski et al 2010a;Koszelewski et al 2008a;Koszelewski et al 2009b).…”

Section: Bioinformatic Data Miningmentioning

confidence: 99%

Features and technical applications of ω-transaminases

Malik

Park

Shin

2012

Appl Microbiol Biotechnol

188

143

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Chiral amines in enantiopure forms are important chemical building blocks, which are most well recognized in the pharmaceutical industries for imparting desirable biological activity to chemical entities. A number of synthetic strategies to produce chiral amines via biocatalytic as well as chemical transformation have been developed. Recently, ω-transaminase (ω-TA) has attracted growing attention as a promising catalyst which provides an environment-friendly access to production of chiral amines with exquisite stereoselectivity and excellent catalytic turnover. To obtain enantiopure amines using ω-TAs, either kinetic resolution of racemic amines or asymmetric amination of achiral ketones is employed. The latter is usually preferred because of twofold higher yield and no requirement of conversion of a ketone product back to racemic amine. However, the choice of a production process depends on several factors such as reaction equilibrium, substrate reactivity, enzyme inhibition, and commercial availability of substrates. This review summarizes the biochemical features of ω-TA, including reaction chemistry, substrate specificity, and active site structure, and then introduces recent advances in expanding the scope of ω-TA reaction by protein engineering and public database searching. We also address crucial factors to be considered for the development of efficient ω-TA processes.

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“…[88] This concept has been applied to a variety of a-chiral primary amines, including the pharmaceutically relevant mexiletine. [89] Very interestingly, a-and w-transaminases have been coupled in a parallel cascade system for the concurrent production of (S)-amino acids and (R)-amines. [90] In this approach, amination of a keto acid with a suitable amino donor affords the corresponding amino acid and a keto acid by-product, which serves as the amino acceptor in the transaminase-catalyzed kinetic resolution of an amine (Scheme 20).…”

Section: Multi-enzymatic Synthesis Of Amines and Amino Acids Employinmentioning

confidence: 99%

Multi‐Enzymatic Cascade Reactions: Overview and Perspectives

Brucher²,

2011

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Multi-enzymatic cascade reactions, i.e., the combination of several enzymatic transformations in concurrent one-pot processes, offer considerable advantages: the demand of time, costs and chemicals for product recovery may be reduced, reversible reactions can be driven to completion and the concentration of harmful or unstable compounds can be kept to a minimum. This review summarizes the developments in multi-enzymatic cascades employed for the asymmetric synthesis of chiral alcohols, amines and amino acids, as well as for C À C bond formation. In addition, a general classification of biocatalytic cascade systems is provided and bioprocess engineering aspects associated with the topic are discussed.

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Deracemization of Mexiletine Biocatalyzed by ω-Transaminases

Cited by 121 publications

References 35 publications

Characterization of a novel amine transaminase from Halomonas elongata

Characterization of a novel amine transaminase from Halomonas elongata

Features and technical applications of ω-transaminases

Multi‐Enzymatic Cascade Reactions: Overview and Perspectives

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