Technical advances towards the industrial application of transaminases for the synthesis of chiral amines
As environmental-friendly thinking starts to reshape our idea of effective and green industrial processes; innovative solutions are emerging rapidly. Around 40% of pharmaceutical compounds contain chiral amine moieties; however, current practices require transition metal catalysts, harsh reaction conditions and suffer from poor selectivity.
In contrast, biocatalysis represents a practical and greener alternative, using naturally occurring enzymes with mild reaction conditions. Transaminases catalyse the asymmetric synthesis of chiral amines from prochiral ketones by using pyridoxal-5’-phosphate (co-factor and an amine donor. In this review we discuss the advances and innovative methods developed to overcome the challenges regarding the general application of TAs at industrial scale, making these biocatalytic systems economically viable and applicable.
An estimated 40% of all pharmaceutical compounds contain chiral amine moieties; therefore, enantiopure amine-synthesis is of great interest (1). Although chemical syntheses are available, these methods usually require transition metal catalysts, harsh reaction conditions and suffer from poor selectivity (2).
In contrast, biocatalysis represents a practical and environmental friendly alternative, using naturally occurring enzymes tailor-made for industrial processes with mild reaction conditions (3). Transaminases (TAs) catalyse the asymmetric synthesis of chiral amines from prochiral ketones, for which pyridoxal-5’-phosphate (PLP) and a suitable amine donor is necessary (4). In addition, they can be used for the kinetic resolution of racemic amines; however, in this case a maximal 50% conversion can be achieved while the enantiomeric excess (ee) is highly dependent on the conversion (2).
The first manufacturing process in the pharmaceutical industry including TAs was for the production of sitagliptin, where the engineered enzyme provided a shorter, more efficient synthesis (5). Since then, a number...