Stereoselectivity of an ω-transaminase-mediated amination of 1,3-dihydroxy-1-phenylpropane-2-one

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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“…Usually, in fact, ,_-dihydroxyketones are not accepted by TAs; two notable exceptions are the -TAs from C. violaceum [22,23] and P.…”

Section:  Amino Acceptor Spectrummentioning

confidence: 99%

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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“…The use of transaminases for the asymmetric synthesis of amines by starting from a prochiral ketone is interesting for interfacing the transamination reaction with the chemical ketone synthesis and different approaches have been described [97,[100][101][102][103][104][105][106][107]. High activity and stability of the transaminase towards the amination of L-erythrulose have been identified as key factors for highefficiency transamination [108,109].…”

Section: Amination Bioprocessesmentioning

confidence: 99%

High-Yield Biocatalytic Amination Reactions in Organic Synthesis

Ward¹,

Wohlgemuth²

2010

COC

142

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The amino functionality gives important biological activity in pharmaceutical compounds. The formation of chiral amines and amino acids can be accomplished by several chemical routes but enzymatic formation of amines offers many advantages in preparing chiral amino compounds or amination of fragile compounds compared to stoichiometric or catalytic chemical transformations. Biocatalytic routes to amines primarily use enzymes of the transaminase class (also known as aminotransferases) which transfer the amino function from a donor organic compound to a ketone or aldehyde acceptor. Although known since 1937, the transamination reaction experiences renewed interest due to the advances in biochemistry and molecular biology and the excellent selectivity of biocatalysts. Other enzymes that have been used to synthesize chiral amines are from the phenylalanine ammonia lyase class that use ammonia as the amino source. The use of recombinant enzymes for the biocatalytic preparation of amines is expanding at a great rate and the range of enzymes revealed in DNA sequence databases is of the order of tens of thousands. Since a large number of substrates like ketones, hydroxyketones and ketoacids can be made by chemical synthesis, the growing toolbox of -, -, -, -, -and -transaminases enable the synthesis of various new chemical entities by biocatalytic amination reactions. In order to simplify the isolation and purification of the product, it is useful to drive the amination reaction to completion. The biocatalytic processes that have been developed show different strategies of overcoming the kinetic limitations of the transaminase reactions and show how some enzymes have been used in processes to make large quantities of chiral compounds with amino functionalities.

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“…The recombinant protein was expressed to high levels and after induction the clarified extract containing just the soluble cell proteins was used directly in biocatalytic conversions with the cofactor pyridoxal 5'-phosphate (PLP). Reactions established that it completely converted (S)--methylbenzylamine and pyruvate to acetophenone and L-Ala, and that it could also convert 1,3-dihydroxy ketones to 2-amino-1,3-diols [61][62][63][64]. The CV2025…”

Section: -Transaminasesmentioning

confidence: 99%

α, α -Dihydroxy Ketones and 2-Amino-1,3-diols: Synthetic and Process Strategies Using Biocatalysts

Hailes¹,

Dalby²,

Lye³

et al. 2010

COC

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There is increasing interest in the use of biocatalysts in synthetic applications due to their ability to achieve highly stereoselective and atom efficient conversions. Recent developments in molecular biology techniques and synthetic biology have also enhanced potential applications using non-natural substrates. Here we review strategies to , '-dihydroxy ketones and 2-amino-1,3-diols via the use of transketolase, a carbon-carbon bond forming biocatalyst, and the enzyme transaminase which converts aldehydes and ketones to amines. Using an integrated strategy we have investigated new chemistries and assays, identified novel biocatalysts and used directed evolution strategies, together with miniaturization studies and modelling to achieve rapid and predictive process scale-up.The use of biocatalysts for the synthesis of biologically active compounds is of increasing interest to the chemical, pharmaceutical and biotechnology sectors in the search for sustainable, cost effective, synthetic strategies. In addition, developments in molecular biology tools and protein and pathway engineering, leading to improved biocatalyst substrate tolerance, specific activities and processing properties are resulting in extensive possibilities for the use of enzymes in synthesis. Current interest in synthetic biology approaches and also cascade reactions, with applications in biofuel synthesis as well as routes to pharmaceuticals, will result in exciting developments and opportunities using biocatalysts in the next decade. At UCL, a multidisciplinary approach has been established in the Departments of Chemistry, Biochemical Engineering and Structural and Molecular Biology (BiCE programme) focusing initially on biocatalytic approaches to , '-dihydroxy ketones and 2-amino-1,3-diols [1]. This has led to the development of new biocatalysts and chemistries and new miniaturization tools for rapid and predictable process scale-up. This review will focus on the use of two enzymes, transketolase (TK) (EC 2.2.1.1) and transaminase (TAm) for the synthesis of the important structural motifs , '-dihydroxy ketones and 2-amino-1,3-diols and biocatalyst scale-up tools.

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Stereoselectivity of an ω-transaminase-mediated amination of 1,3-dihydroxy-1-phenylpropane-2-one

Cited by 48 publications

References 30 publications

Characterization of a novel amine transaminase from Halomonas elongata

Characterization of a novel amine transaminase from Halomonas elongata

High-Yield Biocatalytic Amination Reactions in Organic Synthesis

α, α -Dihydroxy Ketones and 2-Amino-1,3-diols: Synthetic and Process Strategies Using Biocatalysts

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Stereoselectivity of an ω-transaminase-mediated amination of 1,3-dihydroxy-1-phenylpropane-2-one

Cited by 48 publications

References 30 publications

Characterization of a novel amine transaminase from Halomonas elongata

Characterization of a novel amine transaminase from Halomonas elongata

High-Yield Biocatalytic Amination Reactions in Organic Synthesis

&#945;, &#945; -Dihydroxy Ketones and 2-Amino-1,3-diols: Synthetic and Process Strategies Using Biocatalysts

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α, α -Dihydroxy Ketones and 2-Amino-1,3-diols: Synthetic and Process Strategies Using Biocatalysts