Prebiotic Environments with Mg2+ and Thiophilic Metal Ions Increase the Thermal Stability of Cysteine and Non-cysteine Peptides

Wet-dry cycles driven by heating to high temper-atures are frequently invoked for the prebiotic synthesis ofpeptides. Similarly, iron-sulfur clusters are often cited as anexample of an ancient catalyst that helped prune early chemicalsystems into metabolic-like pathways. Because extant iron-sulfurclusters are metallocofactors of protein enzymes and nearlyubiquitous across biology, a reasonable hypothesis is that prebioticiron-sulfur peptides formed on the early Earth. However, iron-sulfur clusters are coordinated by multiple cysteine residues, andthe stability of cysteines to the heat steps of wet-dry cycles has notbeen determined. It, therefore, has remained unclear if the peptidesneeded to stabilize the formation of iron-sulfur clusters could haveformed. If not, then iron-sulfur-dependent activity may haveemerged later, when milder, more biological-like peptide synthesis machinery took hold. Here, we report the thermal stability ofcysteine-containing peptides. We show that temperatures of 150 degrees C lead to the rapid degradation of cysteinyl peptides. However, thepresence of Mg2+at environmentally reasonable concentrations leads to significant protection. Thiophilic metal ions also protectagainst degradation at 150 degrees C but require concentrations not frequently observed in the environment. Nevertheless, cysteine-containing peptides are stable at lower, prebiotically plausible temperatures in seawater, carbonate lake, and ferrous lake conditions.The data are consistent with the persistence of cysteine-containing peptides on the early Earth in environments rich in metal ions.High concentrations of Mg2+are common intra- and extra-cellularly, suggesting that the protection afforded by Mg2+may reflectconditions that were present on the prebiotic Earth.