Metals promote sequences of the reverse Krebs cycle

The rTCA cycle (also known as the reverse Krebs cycle) is a central anabolic biochemical pathway whose origins are proposed to trace back to geochemistry, long before the advent of enzymes, RNA or cells, and whose imprint still remains intimately embedded in the structure of core metabolism. If it existed, a primordial version of the rTCA cycle would necessarily have been catalyzed by naturally occurring minerals at the earliest stage of the transition from geochemistry to biochemistry. Here we report non-enzymatic promotion of multiple reactions of the rTCA cycle in consecutive sequence, whereby 6 of its 11 reactions are promoted by Zn(2+), Cr(3+) and Fe(0) in an acidic aqueous solution. Two distinct three-reaction sequences can be achieved under a common set of conditions. Selectivity is observed for reduction reactions producing rTCA cycle intermediates compared to those leading off-cycle. Reductive amination of ketoacids to furnish amino acids is observed under similar conditions. The emerging reaction network supports the feasibility of primitive anabolism in an acidic, metal-rich reducing environment.