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Review
. 2023 Jul 19;3(8):2073-2085.
doi: 10.1021/jacsau.3c00263. eCollection 2023 Aug 28.

Enabling Broader Adoption of Biocatalysis in Organic Chemistry

Evan O Romero  1 , Anthony T Saucedo  1 , José R Hernández-Meléndez  1 , Di Yang  1 , Suman Chakrabarty  1 , Alison R H Narayan  1
Affiliations
Review

Enabling Broader Adoption of Biocatalysis in Organic Chemistry

Evan O Romero et al. JACS Au. .

Abstract

Biocatalysis is becoming an increasingly impactful method in contemporary synthetic chemistry for target molecule synthesis. The selectivity imparted by enzymes has been leveraged to complete previously intractable chemical transformations and improve synthetic routes toward complex molecules. However, the implementation of biocatalysis in mainstream organic chemistry has been gradual to this point. This is partly due to a set of historical and technological barriers that have prevented chemists from using biocatalysis as a synthetic tool with utility that parallels alternative modes of catalysis. In this Perspective, we discuss these barriers and how they have hindered the adoption of enzyme catalysts into synthetic strategies. We also summarize tools and resources that already enable organic chemists to use biocatalysts. Furthermore, we discuss ways to further lower the barriers for the adoption of biocatalysis by the broader synthetic organic chemistry community through the dissemination of resources, demystifying biocatalytic reactions, and increasing collaboration across the field.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Select examples of chemical structures accessed by using biocatalysis. (A) Compounds formed through C–C bond forming reactions. (B) Compounds accessed using C–H hydroxylation reactions. (C) Hydroxylative dearomatization in the total synthesis of azaphilone natural products. (D) Amino acid C–H hydroxylation in the synthesis of manzacidin C. (E) Multienzyme cascade toward the process-scale total synthesis of islatravir.
Figure 2
Figure 2
(A) Historical access to enzymes and enzyme products was a time-consuming process. The understanding of biological systems and the lack of enabling technologies make it difficult to efficiently develop new biocatalysts. (B) Example of an early application of biocatalysts in the synthesis of d-amino acids. This process required the use of a specific strain of bacteria to complete the transformation.
Figure 3
Figure 3
Accessing biocatalysts with today’s methods. (A) General workflow for producing enzymes from the gene encoding for an enzyme of interest. The various entry points where a scientist could step into the process are highlighted. (B) Enzymes can be used in biocatalytic reactions at various levels of purity.
Figure 4
Figure 4
Chemoenzymatic synthesis of Molnupiravir demonstrated by Merck (right) compared to the previous small-molecule route (left).
Figure 5
Figure 5
Example of a chemoenzymatic synthesis used in an undergraduate chemistry laboratory course.
Figure 6
Figure 6
Examples of chemoenzymatic and enzymatic methods that result from collaborations between organic and biocatalysis research groups.
See this image and copyright information in PMC

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