Industrially Relevant Enzyme Cascades for Drug Synthesis and Their Ecological Assessment

Abstract

Environmentally friendly and sustainable processes for the production of active pharmaceutical ingredients (APIs) gain increasing attention. Biocatalytic synthesis routes with enzyme cascades support many stated green production principles, for example, the reduced need for solvents or the biodegradability of enzymes. Multi-enzyme reactions have even more advantages such as the shift of the equilibrium towards the product side, no intermediate isolation, and the synthesis of complex molecules in one reaction pot. Despite the intriguing benefits, only a few enzyme cascades have been applied in the pharmaceutical industry so far. However, several new enzyme cascades are currently being developed in research that could be of great importance to the pharmaceutical industry. Here, we present multi-enzymatic reactions for API synthesis that are close to an industrial application. Their performances are comparable or exceed their chemical counterparts. A few enzyme cascades that are still in development are also introduced in this review. Economic and ecological considerations are made for some example cascades to assess their environmental friendliness and applicability.

Microbial Lipases and Their Potential in the Production of Pharmaceutical Building Blocks

“…Finally, although microbial lipases could be considered one of the most versatile, they alone can hardly reach the ideal goal of a predominant enzyme synthesis of an API, especially if they involve redox steps; thus, it is necessary to explore the development of enzyme cascades which include the aspects previously listed [ 236 , 237 , 238 , 239 ]. Indeed, the implementation of enzyme cascades in the synthesis of APIs with possibilities of industrial exploitation were recently reviewed [ 240 ]. Standing out in these was the synthesis of Molnupiravir for the treatment of COVID-19, where the immobilized CAL B lipase (Novozym ® 435) participates.…”

Debottlenecking of an In Vitro Enzyme Cascade Using a Combined Model‐ and Experiment‐Based Approach

“…The interest in in vitro enzyme cascades has increased in recent decades and more and more attempts on cascade assemblies are performed [19]. Applications cover a broad field from the synthesis of complex high value compounds such as natural products or active pharmaceutical ingredients to bulk chemicals.…”

Biological activity of new bioactive steroids deriving from biotransformation of cortisone

“…Furthermore, this microorganism-based approach allows to modify starting molecules exploiting several advantages over chemical synthesis, such as the regio- and/or stereospecificity of the reactions. Despite the exciting advantages, only a few biotransformation-based approaches have been applied in the pharmaceutical industry so far [ 20 ]. A recent study reported the production of two new steroid compounds (coded SCA and SCB), not chemically synthesizable, by the biotransformation of cortisone [ 15 ].…”