Engineering and design of artificial enzymes for non-natural biocatalysis in whole cells.

Authors

Hanchen Zhao, Qiqi Liu, Juan Guo, Shuangxi Gu

Published in

Biotechnology advances. Pages 109024. Aug 23, 2026. Epub Aug 23, 2026.

Abstract

Artificial enzymes represent transformative biocatalysts that overcome the inherent limitations of natural enzymes in substrate scope and activity specificity, enabling challenging new-to-nature reactions. Despite remarkable advances in designing diverse artificial enzymes through synthetic cofactor or non-canonical amino acid incorporation, their widespread industrial application remains hindered by the high costs and operational complexity of in vitro systems. Whole-cell biocatalysis emerges as a promising alternative by capitalizing on the cellular environment, including cofactor regeneration, multi-enzyme cascades, and enhanced enzyme stability. This review provides a comprehensive introduction to recent progress in artificial enzyme design and their successful applications in whole-cell biocatalysis. We summarize innovative protein engineering tools for creating artificial enzymes, assembly strategies to enhance in vivo catalytic performance, and representative applications of artificial enzymes-containing whole-cell systems in non-natural transformations. We also discuss the challenges and prospects of whole-cell artificial enzyme catalysis in advancing sustainable and scalable biomanufacturing.

PMID:
42633885
Bibliographic data and abstract were imported from PubMed on 24 Aug 2026.

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