Organic cofactors as connection between minerals and protometabolism?

We can connect the metabolism of the first cells on Earth (Last Universal Common Ancestor, LUCA) to its geochemical roots through top-down comparative bioinformatics[1] and through bottom up geochemical laboratory studies, using minerals and inorganic redox partners (H2, metal ions) as predecessors of enzymes [2]. Our aim is to connect central metabolic cofactors and enzymatic reactions that were present in LUCA to early Earth geochemical reaction partners in order to better understand the transition from environmental reactions to genetically encoded metabolic functions. The hypothesis: cofactors are the missing link between abiotic and biotic (enzymatic) catalysis.In the presented studies, we focus on bridging abiotic and biotic hydrogen/electron transfer. Hydrogen gas, H2, is generated in various geochemical settings, among them serpentinization, a water-rock interaction process during which iron-containing minerals transfer electrons to the protons of water. H2 is also the electron donor for the most ancient route of biological CO2 fixation, the acetyl-CoA pathway. In metabolism itself, H2 is being transformed into biochemical electron donors, cofactors such as the dinucleotide NADH which can be seen – simply put – as hydride (H-) donors. We successfully activated hydrogen on minerals found in serpentinizing systems to reduce NAD+ to NADH under aqueous conditions [3].We transferred these principles onto other biochemical electron acceptors such as flavins and have furthermore shown unexpected mechanistic differences between the reduction of di- and mononucleotides.Our results establish a connection between central reactions in metabolism and abiotic, geochemical catalysis with hydrogen as a common denominator.  References  [1]       M. C. Weiss et al. (2016) Nat. Microbiol. 1, 16116.[2]       M. Preiner et al. (2020) Nat. Ecol. Evol. 4, 534–542.[3]       S. Q. Lang, et al. (2010) Geochim. Cosmochim. Acta. 74, 941–952.[4]       D. P. Pereira et al. (2022) FEBS J. 289, 3148–316.martina.preiner@mpi-marburg.mpg.de Keywords: hydrogen ● cofactors ● minerals ● catalysis ● serpentinization