The Hitchhiker's guide to biocatalysis: recent advances in the use of enzymes in organic synthesis

Abstract

Enzymes are excellent catalysts that are increasingly being used in industry and academia. This Perspective provides a general and practical guide to enzymes and their synthetic potential, primarily aimed at synthetic organic chemists.

Organic solvent stability and long‐term storage of myoglobin‐based carbene transfer biocatalysts

“…As a prominent example, a multienzyme cascade process involving a total of nine enzymes, five of which were modified via protein engineering, was recently implemented by Merck for the large-scale synthesis of the anti-HIV drug islatravir, providing a much shorter and more efficient route for the production of this molecule compared with previously reported synthetic routes [10]. In addition to the desired activity and selectivity, an important requirement for the application of enzymes in industrial and large-scale processes is an inherent (or acquired) stability in the presence of organic solvents, since high concentration of organic co-solvents are often required to solubilize lipophilic substrates and/or achieve high substrate loadings [2,4,[11][12][13][14]. For example, a recently implemented industrial-scale biocatalytic process for the production of the antidiabetic drug sitagliptin involved an engineered transaminase capable of operating in the presence of 50% (v/v) dimethyl sulfoxide (DMSO), which was necessary to permit the use of high substrate loadings (100 g/L) [15].…”

Semi-Continuous Flow Biocatalysis with Affinity Co-Immobilized Ketoreductase and Glucose Dehydrogenase

“…However, the concentration of 100 mM ( Figure 3 ) was inhibited at the 5th hour and achieved only 40.2% after 24 h of biotransformation (data not shown). Ethyl-2-methylacetoacetate and similar types of substrates are often used at low concentrations (25–50 mM) due to their potential to inhibit enzymes [ 48 ].…”

Is it time for biocatalysis in fragment-based drug discovery?

“…Biocatalysts are naturally occurring catalysts that operate with high selectivity. 25 Their inherently selective nature makes enzymes perfect candidates for fragment generation, delivering small, poly-functional molecules without the need for protecting-group chemistry. The number of available biocatalysts has been signicantly expanded by the advent of directed evolution in the early 1990s.…”