Enzymatic C-H activation of aromatic compounds through CO2 fixation

Godwin Aleku, Annica Saaret, Ruth Bradshaw Allen, Sasha Derrington, Gabriel Titchiner, Irina Gostimskaya, Deepanker Gahloth, David A. Parker, Sam Hay, David Leys

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The direct C-H carboxylation of aromatic compounds is an attractive route to the corresponding carboxylic acids, but remains challenging under mild conditions. It has been proposed that the first step in the anaerobic microbial degradation of recalcitrant aromatic compounds is a UbiD-mediated carboxylation. In this study, we use the UbiD-enzyme, ferulic acid decarboxylase in combination with a carboxylic acid reductase to create aromatic degradation inspired cascade reactions. These lead to efficient functionalization of styrene through CO2 fixation. We reveal that rational structure-guided laboratory evolution can expand the substrate scope, resulting in activity on a range of mono- and bi-cyclic aromatic compounds through a single mutation. Selected variants demonstrate a 150-fold improvement in the coumarillic acid to benzofuran + CO2 conversion and unlock reactivity towards naphthoic acid. Our data demonstrates that UbiD-mediated C-H activation is a versatile tool for the transformation of aryl/alkene compounds and CO2 into commodity chemicals.
Original languageEnglish
Pages (from-to)1255-1260
Number of pages6
JournalNature chemical biology
Issue number11
Early online date27 Jul 2020
Publication statusPublished - 1 Nov 2020


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