2026 LIFE RCN Seminar Series Episode 2: Dr. Maria Preiner and Oskari Lehtinen, MSc
Time: February 11th, 8AM PT/11AM ET/5PM CET
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Dr. Martina Preiner
Title: Coenzymes as connection between mineral-
based and enzymatic catalysis en route to
protometabolism
The last universal common ancestor (LUCA) arose in an environment of rocks and water on the early Earth about 4 billion years ago. Top-down comparative bioinformatics reveal LUCA’s carbon metabolism: the acetyl-CoA (or Wood-Ljungdahl) pathway, driven by CO2 and H2 gas. Looking at abiotic, mineral-assisted organic syntheses occurring in hydrothermal vents today, we see how they resemble segments of the pathway, possibly revealing LUCA’s geochemical roots. In order to connect undirected, mineral-assisted catalysis with the complex enzymatic catalysis in LUCA (and extant biochemistry), we are zooming in on central metabolic organic cofactors, so helper molecules employed by enzymes. Examples also found in the acetyl-CoA pathway are nicotinamide adenosine dinucleotide (NAD), C1 donors and acceptors such as tetrahydrofolate (H4F) or, the namesake of the pathway, coenzyme A (CoA). Cofactors have been hypothesized to predate enzymes, so in other words: cofactors could be the missing link between abiotic and biotic (enzymatic) catalysis.
We now show how cofactors employed in the acetyl-CoA pathway can function under conditions found in
serpentinizing systems, where nickel- and iron-containing minerals transfer electrons to the protons of
water, continuously producing hydrogen gas (H2) – LUCA’s main electron and energy source. As one
example, we show how activated hydrogen on minerals found in serpentinizing systems reduces the
central redox cofactor nicotinamide adenosine dinucleotide (NAD). We can furthermore make
assessments on how the structure of NAD enables specific reduction under geochemical conditions,
proposing a pre-enzymatic role of the adenosine monophosphate (AMP) moiety. Such results show how
organic cofactors could play a central role in the transition between mineral and enzymatic catalysis.
Oskari Lehtinen, MSc
Title: Flavin Reduction under prebiotic conditions
While extant life has come far from its origins, it might still hold onto relics and clues of its geochemical beginnings. These links between geo- and biochemistry can still be observed in the metabolism of autotrophic acetogens and methanogens. In their carbon metabolism, the Wood-Ljungdahl pathway, they utilize hydrogen as an energy source and carbon dioxide as a carbon source. This pathway was already present in the Last Universal Common Ancestor (LUCA), the last cell we can obtain via phylogenetics, starting from extant life. While the exergonic reaction between CO2 and H2 would not happen spontaneously due to kinetic hindrances, transition metal-containing minerals can be used as pre-
enzymatic catalysts, yielding intermediates and products of the Wood-Ljungdahl pathway, possibly
showing a geochemical core around which life emerged. However, bridging the gap between mineral
catalysis and enzymatic catalysis remains an unanswered question. We are looking into the role of
coenzymes, so helper molecules of enzymes that often perform the actual chemistry of the catalyzed
reaction, in this transition.
Flavins are redox coenzymes known for their ubiquitous role in a variety of crucial metabolic processes.
We have investigated the abiotic reduction of flavin adenine dinucleotide (FAD) and its truncated version
lacking the adenosine monophosphate, flavin mononucleotide (FMN), under hydrothermal conditions
(40 °C, 5 bar H2 or Ar, phosphate or carbonate buffer). Different pHs, native metals, and minerals were
tested to triangulate the range of conditions in which flavins function. Our results show increasing
reduction with a lower pH environment, and nickel’s (Ni) catalysing ability it is able to promote flavin
reduction in the presence of H2, even in higher pHs where iron (Fe) cannot – most likely because Ni
enables direct hydride (H-) transfer. These findings highlight the importance of the mineral environment’s
context, and also the versatility and capabilities of the flavins to operate under multiple different pHs, and
how they could have linked the motile part of prebiotic chemical networks’ electron transportation with
the immobile environment of a serpentinizing hydrothermal system.