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Abstract Billions of years of evolution have led to the selection of (hyper)thermophiles capable of flourishing at elevated temperatures. The corresponding native (hyper)thermophilic enzymes retain their tertiary and quaternary structures at near‐boiling water temperatures and naturally retain catalytically competent conformational dynamics under these conditions. And yet, while hyper/thermophilic enzymes offer special opportunities in biocatalysis and in hybrid bio/chemocatalytic approaches to modern synthesis in both academia and industry, these enzymes remain underexplored in biocatalysis. Among the strategic advantages that can be leveraged in running biocatalytic transformations at higher temperatures are included more favorable kinetics, removal of volatile byproducts to drive reactions forward, improved substrate solubility and product separation, and accelerated stereodynamics for dynamic kinetic resolutions. These topics are discussed and illustrated with contemporary examples of note, in sections organized by stratagem. Finally, the reader is alerted in particular to archaeal enzymes that have proven useful in non‐natural synthetic chemistry ventures, and at the same time is referred to a rich area of archaea whose genomes have been sequenced but whose enzymatic activities of interest have not yet been mined. Though hyperthermophilic archaea are among the most ancient of organisms, their enzymes may hold the key to many future innovations in biocatalytic chemistry–perhaps we really do need to go ‘back to the future’.
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Catalyzing the future: recent advances in chemical synthesis using enzymes
Biocatalysis has the potential to address the need for more sustainable organic synthesis routes. Protein engineering can tune enzymes to perform in cascade reactions and for efficient synthesis of enantiomerically enriched compounds, using both natural and new-to-nature reaction pathways. This review highlights recent achievements in biocatalysis, especially the development of novel enzymatic syntheses to access versatile small molecule intermediates and complex biomolecules. Biocatalytic strategies for the degradation of persistent pollutants and approaches for biomass valorization are also discussed. The transition of chemical synthesis to a greener future will be accelerated by implementing enzymes and engineering them for high performance and new activities.
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- Award ID(s):
- 2016137
- PAR ID:
- 10584692
- Editor(s):
- Cornish, Virginia; Billerbeck, Sonja
- Publisher / Repository:
- Current Opinion in Chemical Biology
- Date Published:
- Journal Name:
- Current Opinion in Chemical Biology
- Edition / Version:
- 1
- Volume:
- 83
- Issue:
- C
- ISSN:
- 1367-5931
- Page Range / eLocation ID:
- 102536
- Subject(s) / Keyword(s):
- Engineered biocatalysts that access pharmaceutical products through more sustainable synthetic routes Novel biocatalysts that construct enantiomerically enriched small-molecule intermediates Complex biomolecules synthesized using enzymatic cascade reactions Biocatalytic degradation of persistent pollutants and valorization of biomass to afford valuable compounds
- Format(s):
- Medium: X Size: 2MB Other: pdf
- Size(s):
- 2MB
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1016/j.cbpa.2024.102536
