Enzymatic carbon dioxide fixation is one of the most
important
metabolic reactions as it allows the capture of inorganic carbon from
the atmosphere and its conversion into organic biomass. However, due
to the often unfavorable thermodynamics and the difficulties associated
with the utilization of CO2, a gaseous substrate that is
found in comparatively low concentrations in the atmosphere, such
reactions remain challenging for biotechnological applications. Nature
has tackled these problems by evolution of dedicated CO2-fixing enzymes, i.e., carboxylases, and embedding them in complex
metabolic pathways. Biotechnology employs such carboxylating and decarboxylating
enzymes for the carboxylation of aromatic and aliphatic substrates
either by embedding them into more complex reaction cascades or by
shifting the reaction equilibrium via reaction engineering. This review
aims to provide an overview of natural CO2-fixing enzymes
and their mechanistic similarities. We also discuss biocatalytic applications
of carboxylases and decarboxylases for the synthesis of valuable products
and provide a separate summary of strategies to improve the efficiency
of such processes. We briefly summarize natural CO2fixation
pathways, provide a roadmap for the design and implementation of artificial
carbon fixation pathways, and highlight examples of biocatalytic cascades
involving carboxylases. Additionally, we suggest that biochemical
utilization of reduced CO2derivates, such as formate or
methanol, represents a suitable alternative to direct use of CO2and provide several examples. Our discussion closes with
a techno-economic perspective on enzymatic CO2fixation
and its potential to reduce CO2emissions.