CoBeEn · Cofactors and Minerals Before Enzymes: Unravelling the Pre-Enzymatic Path of Autotrophic CO2 Fixation

There are two approaches to the emergence of life: bottom up and top down. This means on one hand, we can start with simple geochemical reactions and try to synthesize increasingly complex molecules and reaction networks from there. On the other hand, we can start with life as we know it and try to decomplicate the chemical reactions that run it to find a common denominator. Both approaches have yielded important insights, but they also have their limitations. So far, the two approaches are far away from ultimately converging. CoBeEN aims to reconcile geochemistry and biochemistry by focussing on the most ancient carbon fixation route: the Wood-Ljungdahl pathway (WLP). This autotrophic pathway uses the electrons of hydrogen to fix CO2, a reaction that also occurs abiotically – using minerals as catalysts instead of enzymes. The mere transition from minerals to enzymes seems far-fetched, given the leap in complexity required. However, organic cofactors or coenzymes, simpler organic molecules assisting enzymatic reactions by being truly recyclable reaction partners, are hypothesized to have preceded enzymes. They are pivotal in theoretical reconstructions of autocatalytic, non-enzymatic networks describing a minimal metabolism based on carbon fixation. CoBeEn postulates that coenzymes played a central role in enabling the transition from mineral-based CO2 fixation to enzymatic carbon metabolism. CoBeEn will experimentally link key metabolic cofactors of the WLP to mineral-assisted catalysis. The goal is to understand the transition from environmental reactions to metabolic functions by elucidating how metabolic pathways and the molecules employed by them were selected by the environment. By mapping the understudied interactions between chemically active environments and metabolism, we will gain insights into their mechanistic interdependencies before they were separated by the origin of cellular organization.