Biocatalysis for Industrial Production of Active Pharmaceutical Ingredients (APIs)

Abstract

From an industrial point of view, biocatalysis is particularly important in the production of active pharmaceutical ingredients (APIs), offering increasingly high demands for regio-, stereo,- and enantioselectivity of drugs. Biocatalytic processes are more ecofriendly, sustainable, and profitable, and hence biocatalysis is proving to be key for the development of the so-called bioeconomy. Thus, in the manufacturing of APIs, as either pharmaceutical products or intermediates, biocatalysis is considered as a “green” technology to efficiently discriminate between isomers in a racemic mixture under mild conditions, compared to chemical salt resolutions which may involve contaminants and are expensive. In addition to enantioselectivity, regioselectivity on complex molecules is another inherent feature of chemoenzymatic processes, which avoids the need of protecting groups, and reduces the number of synthetic steps. Finally, biocatalysis can also be used to produce achiral APIs where classical chemical methods are too complicated. Therefore, a huge number and quantity of enzymes are now available in the market (Reetz, 2013). Although isolated enzymes are mainly chosen for their simple implementation in biocatalyzed processes, whole-cell biotransformations are generally preferred for complex reactions involving more than one enzyme or cofactor, or for reactions where enzymes are not suitable for isolation. We herein provide examples of the application of isolated enzymes (wild-type or mutants) and whole cells, either in soluble or immobilized form, in the synthesis of some valuable APIs.