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 anaerobic microbial degradation of recalcitrant aromatic compounds is a UbiD-mediated carboxylation. In this study, we use the UbiD enzyme ferulic acid decarboxylase (Fdc) in combination with a carboxylic acid reductase to create aromatic degradation-inspired cascade reactions, leading to efficient functionalization of styrene through CO₂ fixation. We reveal that rational structure-guided laboratory evolution can expand the substrate scope of Fdc, resulting in activity on a range of mono- and bicyclic aromatic compounds through a single mutation. Selected variants demonstrated 150-fold improvement in the conversion of coumarillic acid to benzofuran + CO₂ and unlocked reactivity towards naphthoic acid. Our data demonstrate that UbiD-mediated C–H activation is a versatile tool for the transformation of aryl/alkene compounds and CO₂ into commodity chemicals.

芳香族化合物直接C–H羧化是获得相应羧酸的诱人途径，但在温和条件下仍具有挑战性。已经提出，难降解的芳族化合物的厌氧微生物降解的第一步是UbiD介导的羧化。在这项研究中，我们将UbiD酶阿魏酸脱羧酶（Fdc）与羧酸还原酶结合使用，以产生芳香族化合物降解的级联反应，从而使苯乙烯通过CO ₂有效官能化固定。我们揭示了合理的结构指导的实验室进化可以扩大Fdc的底物范围，从而通过单个突变对一系列单环和双环芳族化合物产生活性。所选的变体显示出香豆酸向苯并呋喃+ CO ₂的转化率提高了150倍，并释放了对萘甲酸的反应性。我们的数据表明，UbiD介导的CH活化是将芳基/烯烃化合物和CO ₂转化为商品化学品的多功能工具。