Natural carbon fixation and advances in synthetic engineering for redesigning and creating new fixation pathways

Abstract

Background: Autotrophic carbon fixation is the primary route through which organic carbon enters the biosphere, and it is a key step in the biogeochemical carbon cycle. The Calvin-Benson-Bassham pathway, which is predominantly found in plants, algae, and some bacteria (mainly cyanobacteria), was previously considered to be the sole carbon-fixation pathway. However, the discovery of a new carbon-fixation pathway in sulfurous green bacteria almost two decades ago encouraged further research on previously overlooked ancient carbon-fixation pathways in taxonomically and phylogenetically distinct microorganisms.

Aim of review: In this review, we summarize the six known natural carbon-fixation pathways and outline the newly proposed additions to this list. We also discuss the recent achievements in synthetic carbon fixation and the importance of the metabolism of thermophilic microorganisms in this field.

Key scientific concepts of review: Currently, at least six carbon-fixation routes have been confirmed in Bacteria and Archaea. Other possible candidate routes have also been suggested on the basis of emerging "omics" data analyses, expanding our knowledge and stimulating discussions on the importance of these pathways in the way organisms acquire carbon. Notably, the currently known natural fixation routes cannot balance the excessive anthropogenic carbon emissions in a highly unbalanced global carbon cycle. Therefore, significant efforts have also been made to improve the existing carbon-fixation pathways and/or design new efficient in vitro and in vivo synthetic pathways.

Keywords: Autotrophic; Biochemistry; Carbon fixation; Omics; Synthetic pathway; Thermophiles.

Graphical abstract

Fig. 1

A timeline summary showing key milestones and findings related to carbon fixation pathways discussed in our work.

Fig. 2

Natural carbon fixation. (A) CBB cycle; enzymes: ribulose-1,5-bisphosphate carboxylase/oxygenase, 3-phosphoglycerate kinase, glyceraldehyde-3-phosphate dehydrogenase, ribulose-phosphate epimerase. (B) rTCA cycle; enzymes: ATP-citrate lyase, malate dehydrogenase, succinyl-CoA synthetase, ferredoxin (Fd)-dependent-2-oxoglutarate synthase, isocitrate dehydrogenase, PEP carboxylase. (C) Wood–Ljungdahl cycle, upstairs acetogens Archaea and downstairs methanogens Archaea; enzymes: MPT-methylene tetrahydromethopterin, MFR-methanofuran, THF, tetrahydrofolate. (D) 3HP cycle; enzymes: acetyl-CoA carboxylase, propionyl-CoA carboxylase, methylmalonyl-CoA epimerase, succinyl-CoA:(S)-malate-CoA transferase, trifunctional (S)-malyl-CoA, -methylmalyl-CoA, mesaconyl-CoA transferase, mesaconyl-C4-CoA hydratase. (E) HP/HP and DC/HP cycle; enzymes: pyruvate synthase, PEP-carboxylase, malate dehydrogenase, fumarate hydratase/reductase, acetyl-CoA/propionyl-CoA carboxylase, 3-hydroxypropionate-CoA ligase/dehydratase, methylmalonyl-CoA mutase, succinyl-CoA reductase, 4-hydroxybutyrate-CoA ligase, crotonyl-CoA hydratase, acetoacetyl-CoA-ketothiolase.