Cascades of Evolved Enzymes for the Synthesis of Complex Molecules
Overview
Affiliations
Thanks to advances in enzyme discovery and protein engineering combined with the development of enzymatic multistep reaction cascades, new efficient routes for drug synthesis have been created that are superior to chemical syntheses. This supports the goal of the chemical and pharmaceutical industries to move to more sustainable and environmentally friendly processes. Recently described outstanding examples include the biocatalytic cascade syntheses of the cyclic dinucleotide MK-1454, molnupiravir, and islatravir, as well as the efficient fixation of CO to make starch using an artificial enzyme cascade.
Multienzyme cascade for synthesis of hydroxytyrosol via engineered Escherichia coli.
Xiong T, Li X, Liu W, Yue H, Liu J, Bai D Sci Rep. 2025; 15(1):471.
PMID: 39748076 PMC: 11696566. DOI: 10.1038/s41598-024-84624-5.
Nguyen D, Zhu L, Gray D, Woods T, Padhi C, Flatt K ACS Cent Sci. 2024; 10(5):1022-1032.
PMID: 38799663 PMC: 11117315. DOI: 10.1021/acscentsci.4c00088.
Genome Mining for New Enzyme Chemistry.
Nguyen D, Mitchell D, van der Donk W ACS Catal. 2024; 14(7):4536-4553.
PMID: 38601780 PMC: 11002830. DOI: 10.1021/acscatal.3c06322.
Nguyen D, Zhu L, Gray D, Woods T, Padhi C, Flatt K bioRxiv. 2023; .
PMID: 37965205 PMC: 10635010. DOI: 10.1101/2023.10.30.564719.
Opportunities and Challenges of Metal-Organic Framework Micro/Nano Reactors for Cascade Reactions.
Wu P, Zhao Y, Zhang X, Fan Y, Zhang S, Zhang W JACS Au. 2023; 3(9):2413-2435.
PMID: 37772189 PMC: 10523373. DOI: 10.1021/jacsau.3c00344.