Molland Daniel P, Rhyu Isabella B, Wade Jon, Schnell Jason R
Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU Oxford, U.K.
Department of Earth Sciences, University of Oxford, South Parks Road, OX1 3AN Oxford, U.K.
JACS Au. 2025 Mar 31;5(4):1922-1931. doi: 10.1021/jacsau.5c00153. eCollection 2025 Apr 28.
Surface-catalyzed peptide bond formation may have been an important source of peptides for abiogenesis, but model peptide synthesis reactions using the consensus set of 10 abiotic amino acids give only modest rates of peptide bond formation. Additionally, the peptides are typically limited in length to a small number of amino acids and stereoselective amino acid incorporation is weak or absent. An abiotic route for the high-yield synthesis of cysteine from serine was recently reported by Foden et al. ( , 370, 865-869), indicating that, in some environments, prebiotic cysteine may also have been available. Here, we show that the presence of cysteine dramatically increases the yields of surface-catalyzed peptide synthesis reactions in a hydrothermal vent solvent model containing achiral silicate minerals and that the reaction exhibits a strong stereoselective bias toward l-cysteine. Solid state NMR confirmed that cysteine associates bivalently with silicates at alkaline pH via both the carboxylate and the sulfur groups. Polarization-resolved IRRAS indicates that the bivalent adsorption stereospecifically orients the reactive amino group, providing a mechanism for stereoselective incorporation of l-cysteine. Stereoselective rates of peptide bond formation in surface-catalyzed peptide bond formation are expected to occur for any amino acid able to form sufficiently strong side chain-silicate interactions at alkaline pH. The high nucleophilicity of the thiol group produces unusually high reaction rates and stereoselectivity in such reactions, in addition to conferring transition metal ion binding to the peptide products. The potential benefits of reactive sulfur species for abiogenesis suggest that they may be useful biosignatures in the search for habitable extraterrestrial environments.
表面催化的肽键形成可能是生命起源中肽的重要来源，但使用10种非生物氨基酸的共识集进行的模型肽合成反应，肽键形成速率仅适中。此外，肽的长度通常限于少数氨基酸，并且立体选择性氨基酸掺入较弱或不存在。Foden等人最近报道了一条从丝氨酸高产合成半胱氨酸的非生物途径（，370, 865 - 869），这表明在某些环境中，益生元半胱氨酸也可能是可获得的。在这里，我们表明半胱氨酸的存在显著提高了在含有非手性硅酸盐矿物的热液喷口溶剂模型中表面催化肽合成反应的产率，并且该反应对L - 半胱氨酸表现出强烈的立体选择性偏向。固态核磁共振证实，在碱性pH值下，半胱氨酸通过羧基和硫基团与硅酸盐二价结合。偏振分辨红外反射吸收光谱表明，二价吸附使反应性氨基立体定向，为L - 半胱氨酸的立体选择性掺入提供了一种机制。对于任何能够在碱性pH值下形成足够强的侧链 - 硅酸盐相互作用的氨基酸，预计在表面催化的肽键形成中会出现肽键形成的立体选择性速率。除了使肽产物与过渡金属离子结合外，硫醇基团的高亲核性在这类反应中产生异常高的反应速率和立体选择性。反应性硫物种对生命起源的潜在益处表明，它们可能是寻找宜居外星环境中有价值的生物标志。
