The Impact of Metagenomics on Biocatalysis

• Published in: Angewandte Chemie International Edition 2024-05, Vol.63 (21), p.e202402316-n/a
• Main Authors: Hogg, Bethany N., Schnepel, Christian, Finnigan, James D., Charnock, Simon J., Hayes, Martin A., Turner, Nicholas J.
• Format: Article
• Language: English
• Subjects: Biocatalysis; Biocatalysts; Catalysis; Enzymes; Enzymes - chemistry; Enzymes - genetics; Enzymes - metabolism; Metagenomics; Minireview; Minireviews; Natural selection; Protein Engineering; Proteins
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202402316

In the ever‐growing demand for sustainable ways to produce high‐value small molecules, biocatalysis has come to the forefront of greener routes to these chemicals. As such, the need to constantly find and optimise suitable biocatalysts for specific transformations has never been greater. Metagenome mining has been shown to rapidly expand the toolkit of promiscuous enzymes needed for new transformations, without requiring protein engineering steps. If protein engineering is needed, the metagenomic candidate can often provide a better starting point for engineering than a previously discovered enzyme on the open database or from literature, for instance. In this review, we highlight where metagenomics has made substantial impact on the area of biocatalysis in recent years. We review the discovery of enzymes in previously unexplored or ‘hidden’ sequence space, leading to the characterisation of enzymes with enhanced properties that originate from natural selection pressures in native environments. Metagenomics generally involves isolation and extraction of DNA from various environmental samples, which can then be cloned and expressed into proteins of interest to address difficult chemical reactions in biocatalysis.