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Review
. 2024 Mar 27;146(12):7876-7884.
doi: 10.1021/jacs.3c09542. Epub 2024 Mar 15.

Multifunctional Biocatalysts for Organic Synthesis

Thomas W Thorpe  1 , James R Marshall  1 , Nicholas J Turner  1
Affiliations
Review

Multifunctional Biocatalysts for Organic Synthesis

Thomas W Thorpe et al. J Am Chem Soc. .

Abstract

Biocatalysis is becoming an indispensable tool in organic synthesis due to high enzymatic catalytic efficiency as well as exquisite chemo- and stereoselectivity. Some biocatalysts display great promiscuity including a broad substrate scope as well as the ability to catalyze more than one type of transformation. These promiscuous activities have been applied individually to efficiently access numerous valuable target molecules. However, systems in which enzymes possessing multiple different catalytic activities are applied in the synthesis are less well developed. Such multifunctional biocatalysts (MFBs) would simplify chemical synthesis by reducing the number of operational steps and enzyme count, as well as simplifying the sequence space that needs to be engineered to develop an efficient biocatalyst. In this Perspective, we highlight recently reported MFBs focusing on their synthetic utility and mechanism. We also offer insight into their origin as well as comment on potential strategies for their discovery and engineering.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Multifunctional Biocatalysts (MFBs) Simplify Chemical Synthesis and Biocatalyst Development for the Conversion of A to B to C
Scheme 2
Scheme 2. Catalytic Cycles of 4-OT Multifunctional Reactions: (a) Aldol Dehydration-Conjugate Addition; (b) Three-Component Cyclization Cascade
Scheme 3
Scheme 3. Catalytic Cycles of ERED Multifunctional Reactions: (a) Asymmetric Reductive Carbocyclization; (b) Asymmetric Intermolecular Photobiocatalytic Hydroalkylation via Tertiary Electron Donor–Acceptor Complex
Scheme 4
Scheme 4. Catalytic Cycles of Multifunctional P450 Reactions: (a) Asymmetric Carbene N–H Insertion; (b) Atom-Transfer Radical Cyclization
Scheme 5
Scheme 5. Catalytic Cycles of Ene-IREDs Multifunctional Reactions: (a) Conjugate Reduction-Reductive Amination; (b) Reduction of Dihydropyridiniums to Piperidines
Scheme 6
Scheme 6. Examples of Multifunctional Enzymes in Metabolic Pathways and Designed Biocatalysts with Complex Mechanisms: (a) the Algal Lipoxygenase; (b) the Short-Chain Dehydrogenase AniN; (c) an Artificial Enzyme with Multiple Synergistic Abiological Active Sites; (d) an Enzyme for the Multistep Morita–Bayliss–Hillman Reaction
See this image and copyright information in PMC

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