- n-Butylamine as an alternative amine donor for the stereoselective biocatalytic transamination of ketones
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Formal reductive amination has been a main focus of biocatalysis research in recent times. Among the enzymes able to perform this transformation, pyridoxal-5′-phosphate-dependent transaminases have shown the greatest promise in terms of extensive substrate scope and industrial application. Despite concerted research efforts in this area, there exist relatively few options regarding efficient amino donor co-substrates capable of allowing high conversion and atom efficiency with stable enzyme systems. Herein we describe the implementation of the recently described spuC gene, coding for a putrescine transaminase, exploiting its unusual amine donor tolerance to allow use of inexpensive and readily-available n-butylamine as an alternative to traditional methods. Via the integration of SpuC homologues with tandem co-product removal and cofactor regeneration enzymes, high conversion could be achieved with just 1.5 equivalents of the amine with products displaying excellent enantiopurity.
- Slabu, Iustina,Galman, James L.,Iglesias, Cesar,Weise, Nicholas J.,Lloyd, Richard C.,Turner, Nicholas J.
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- Biocatalytic transamination with near-stoichiometric inexpensive amine donors mediated by bifunctional mono- and di-amine transaminases
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The discovery and characterisation of enzymes with both monoamine and diamine transaminase activity is reported, allowing conversion of a wide range of target ketone substrates with just a small excess of amine donor. The diamine co-substrates (putrescine, cadaverine or spermidine) are bio-derived and the enzyme system results in very little waste, making it a greener strategy for the production of valuable amine fine chemicals and pharmaceuticals.
- Galman, James L.,Slabu, Iustina,Weise, Nicholas J.,Iglesias, Cesar,Parmeggiani, Fabio,Lloyd, Richard C.,Turner, Nicholas J.
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supporting information
p. 361 - 366
(2017/08/14)
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- Transaminases applied to the synthesis of high added-value enantiopure amines
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Critical parameters affecting the stereoselective amination of (hetero)aromatic ketones using transaminases have been studied, such as temperature, pH, substrate concentration, cosolvent, and source and percentage of amino donor, to further optimize the production of enantiopure amines using both (S)- and (R)-selective biocatalysts from commercial suppliers. Interesting enantiopure amino building blocks have been obtained, overcoming some limitations of traditional chemical synthetic methods. Representative processes were scaled up, affording halogenated and heteroaromatic amines in enantiomerically pure form and good isolated yields.
- Paul, Caroline E.,Rodriguez-Mata, Maria,Busto, Eduardo,Lavandera, Ivan,Gotor-Fernandez, Vicente,Gotor, Vicente,Garcia-Cerrada, Susana,Mendiola, Javier,De Frutos, Oscar,Collado, Ivan
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supporting information
p. 788 - 792
(2014/07/08)
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