Enzyme-Mediated Carbon Dioxide Fixation: Catalytic Mechanisms and Computational Insights

ABSTRACT: Carbon conversion technologies that transform carbon dioxide (CO₂) into high-value chemicals are pivotal for achieving sustainability. Among these, enzyme-mediated CO₂ fixation has recently gained increasing attention as a more sustainable and environmentally friendly alternative to traditional chemical methods, which typically require harsh conditions and impose significant environmental costs. Recent advances in computer-aided techniques have greatly facilitated the mechanistic understanding of CO₂-fixing enzymes and accelerated the development of enzyme-catalyzed carboxylation strategies. This review highlights recent progress in enzyme-mediated CO₂ fixation by categorizing key enzymes into four classes based on their cofactor or metal ion requirements: cofactor-independent enzymes, metal-dependent enzymes, nicotinamide adenine dinucleotide phosphate (NAD(P)H)-dependent enzymes, and prenylated flavin mononucleotide (prFMN)-dependent enzymes. We outline the basic principles and applications of molecular dynamics (MD) simulations and quantum mechanical (QM) calculations, which serve as essential tools for investigating enzyme conformational dynamics and reaction mechanisms. Through representative case studies, we demonstrate how computational analyses uncover catalytic features that enhance CO₂ conversion efficiency. These insights underscore the critical role of computer-aided approaches in guiding the rational design and optimization of biocatalysts, thereby advancing the application of enzyme-based systems for CO₂ fixation.