Rizzo, Andrea;
Aranda, Carmen;
Galman, James;
Alcasabas, Annette;
Pandya, Akash;
Bornadel, Amin;
Costa, Bruna;
... Dominguez, Beatriz; + view all
(2024)
Broadening The Substrate Scope of Aldolases Through Metagenomic Enzyme Discovery.
ChemBioChem
, Article e202400278. 10.1002/cbic.202400278.
(In press).
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Abstract
Bio-processes based on enzymatic catalysis play a major role in the development of green, sustainable processes, and the discovery of new enzymes is key to this approach. In this work, we analysed ten metagenomes and retrieved 48 genes coding for deoxyribose-5-phosphate aldolases (DERAs, EC 4.1.2.4) using a sequence-based approach. These sequences were recombinantly expressed in Escherichia coli and screened for activity towards a range of aldol additions. Among these, one enzyme, DERA-61, proved to be particularly interesting and catalysed the aldol addition of furfural or benzaldehyde with acetone, butanone and cyclobutanone with unprecedented activity. The product of these reactions, aldols, can find applications as building blocks in the synthesis of biologically active compounds. Screening was carried out to identify optimized reaction conditions targeting temperature, pH, and salt concentrations. Lastly, the kinetics and the stereochemistry of the products were investigated, revealing that DERA-61 and other metagenomic DERAs have superior activity and stereoselectivity when they are provided with non-natural substrates, compared to well-known DERAs.
| Type: | Article |
|---|---|
| Title: | Broadening The Substrate Scope of Aldolases Through Metagenomic Enzyme Discovery |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/cbic.202400278 |
| Publisher version: | http://dx.doi.org/10.1002/cbic.202400278 |
| Language: | English |
| Additional information: | © 2024 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
| Keywords: | DERA, Aldol reaction, biocatalysis, metagenome, furfural |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10197393 |
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