CO2 Fixation and Energy Conservation in the ancient Wood-Ljungdahl Pathway

Carbon dioxide (CO2) receives a lot of attention as a greenhouse gas that promotes human-induced climate change. On the other hand, CO2 is also the starting point for the production of virtually all biomass on our planet. Therefore, nature has developed sophisticated methods to fix CO2 and make it available for biochemical reactions. Of all known biological CO2 fixation pathways, the Wood-Ljungdahl pathway (WLP) is the simplest way to fix two CO2 molecules to form acetyl-CoA, the key metabolic intermediate for biomass formation. It is the only pathway directly related to energy conservation and regarded to be the be the most ancient. The Two-CO2-One project aims to gain a comprehensive structural and mechanistic understanding of CO2 fixation and energy conservation in acetogenic bacteria and methanogenic archaea. These ecologically highly relevant organisms can live under conditions of extreme energy limitation in the absence of oxygen and feed exclusively on CO2 and hydrogen. I will elucidate how these species fix CO2 and conserve energy through their WLP by using the innovative structural approach of redox-guided cryogenic electron microscopy (Cryo-EM) to study the oxygen-sensitive metalloprotein machinery of the WLP. The mechanistic insights gained will be challenged by microbiological and genetic approaches in these anaerobic, non-standard model organisms.Using autotrophic organisms that can sequester gaseous CO2 to produce biogas or ethanol from abundant waste gas resources is one way to reduce the human carbon footprint. Therefore, the Two-CO2-One project will not only lead to a deeper understanding of the unique mechanistic principles of WLP, but also provide new perspectives for developing biotechnological applications based on improved microbes that capture and sequester CO2 to produce industrially relevant chemicals and to combat human-induced climate change.