Metabolism without enzymes: from geochemistry to understanding the origin of life.

Understanding the chemical origin of life depends on a few fundamental, long-unresolved questions: how to explain the emergence of biomolecules from simple abiotic substrates? How did biochemical complexity develop before the advent of enzymes, RNA/DNA and cells? Most experimental work in the area to date has been focused on producing biomolecules via synthetic routes and systems chemistry that are very different from the way core metabolism functions.^1,2 An alternative hypothesis is that two biological CO2-fixing pathways, the reductive AcCoA pathway and the reductive tricarboxylic acid (rTCA) cycle, are "chemical fossils" of the prebiotic pathways that functioned at the earliest stages of the origins of life.³

In this talk, I will present the process of discovering how the entire reductive AcCoA pathway and more than half of the rTCA cycle may be promoted under a common, mild set of conditions, by simple metals and metal ions.^4,5 Is it a coincidence that the enzymes associated with these reactions use the very same metals in their active sites?^6,7 Next, I will hypothesise whether surface chemistry, potentially operating in the non-enzymatic AcCoA pathway,⁵ can be extended towards more complex reactions that branch out of the rTCA cycle, such as a non-enzymatic gluconeogenesis.⁸ One possible approach is the study of dynamic gas-water-mineral-ice interfaces^9,10 with the goal to promote a non-enzymatic gluconeogenesis under uniform, geochemically plausible conditions.

¹ Sutherland, J.D. Angew. Chem. Int. Ed., 2016, 55, 104
² Patel B. H., Percivalle C., Ritson D. J., Duffy, C. D., Sutherland, J. D. Nat. Chem. 2015, 7, 301.
³ Braakman R., Smith E. PLoS Comp. Biol. 2012, 8, e1002455
⁴ Muchowska K.M., Varma S.J., Chevallot-Beroux E., Lethuillier-Karl L., Li G. Moran, J. Nat. Eco. Evo., 2017, 10.1038/s41559-017-0311-7
⁵ Varma S. J., Muchowska K. B., Chatelain P., Moran J., submitted
⁶ Nitschke W., McGlynn S. E., Milner-White, E. J., Russell, M. J. Biochim Biophys Acta, 2013, 1827, 871
⁷ Sousa F.L., Martin W. F. Biochim Biophys Acta. 2014, 1837, 964
⁸ Messner C.B., Driscoll P.C., Piedrafita G., De Volder M.F.L., Ralser M. P. Natl. Acad. Sci., 2017, 114, 7403
⁹ Trinks H., Schröder W., Biebricher C.K. Orig. Life Evol. Biosph., 2005, 35, 429
¹⁰ Menor-Salván, C., Marín-Yaseli, M.R., Chem. Soc. Rev., 2012, 41, 5404