10:45 〜 11:00
[U12-06] Prebiotic cyanide generation from amino acids
★Invited Papers
キーワード：Origin of Life、Prebiotic chemistry、Amino acid chemistry、Cyanide formation
The pioneering work by Miller-Urey for amino acid synthesis and Oró for purine synthesis established the foundation of current understanding of constructing biological building blocks for the origin of life (OoL) from simple and reactive molecules. One of the key components in modern prebiotic chemistry is hydrogen cyanide (HCN) which has been demonstrated to synthesize amino acids, nucleobases, lipid precursors and pentose. In the meanwhile, new functions of HCN has been progressively identified, strengthening its critical role in establishing the early metabolism. As a result, HCN is recognized as a central molecule for the molecular evolution of early prebiotic chemical networks and OoL.
However, sufficient HCN supply for the above-mentioned chemistry to take place sustainably on early Earth remains experimentally elusive. Previous attempts to rationalize the HCN emergence by simulation follows geological settings of Miller-Urey’s experiment which is rich in methane and ammonia under a reducing atmosphere. While simulation and limited experiments have demonstrated that such gas composition did produce HCN by discharge and photo-illumination. The key starting molecule, methane, has been considered as a minor component of Hadean atmosphere, therefore, the contribution of atmospheric synthesis of HCN is insufficient to sustain prebiotic chemical evolution.
Another more promising scenario for HCN generation under atmosphere with redox-neutral gases (CO2, CO, N2) has been recently proposed. The scenario simulated that mid-size meteorite impact during the late-bombardment period generates HCN more efficiently than photochemically produced HCN from methane with experimental demonstration of such event on laboratory base.
Here, we report the cyanide formation via oxidation of amino acids by geological available minerals. Using glycine as a representative amino acid substrate, we found that this reaction could take place under wide ranges of pH (2-13) and temperature (6 – 60 ℃). This oxidation reaction was monitored to reach equilibrium within 24 hours and the minimum amount of glycine required for cyanide generation could be decreased to 1 mM with a yield of 47%. Isotopic labeling experiment using UPLC-ESI-MS identified that cyanide was produced from 2-C position of glycine through a C-C bond cleavage pathway. And kinetic isotope experiment revealed that α-proton abstraction plays a crucial role in initiating this reaction. In addition to glycine, amino acid oxidation by natural mineral could be applied to all the 20 proteogenic amino acids and poly peptides of glycine. Product distribution varies with amino acids, but seven out of twenty amino acids have been identified to be active to generate cyanide. Ammonia and organic carboxylic acids appeared to be commonly produced from corresponding amino acids. Furthermore, intermediates of reductive Kreb’s Cycle (rTCA cycle), including pyruvate, oxaloacetate, keto-glutarate, succinate, fumarate, were detected from alanine, aspartate or glutamate.
The robustness of cyanide production from amino acids described here for the first time demonstrated a pathway independent of gaseous components of early atmosphere with detailed experimental investigation. It has been extensively studied that amino acids can be produced via multiple mechanisms and starting material throughout Earth history. Therefore, amino acids as alternative source of HCN offer great advantages due to the easy accessibility of diverse amino acid sources. We hope our discovery contributes to the current studies of prebiotic chemistry, especially HCN-based chemistry, by providing an efficient, robust and simple HCN generation pathway.
However, sufficient HCN supply for the above-mentioned chemistry to take place sustainably on early Earth remains experimentally elusive. Previous attempts to rationalize the HCN emergence by simulation follows geological settings of Miller-Urey’s experiment which is rich in methane and ammonia under a reducing atmosphere. While simulation and limited experiments have demonstrated that such gas composition did produce HCN by discharge and photo-illumination. The key starting molecule, methane, has been considered as a minor component of Hadean atmosphere, therefore, the contribution of atmospheric synthesis of HCN is insufficient to sustain prebiotic chemical evolution.
Another more promising scenario for HCN generation under atmosphere with redox-neutral gases (CO2, CO, N2) has been recently proposed. The scenario simulated that mid-size meteorite impact during the late-bombardment period generates HCN more efficiently than photochemically produced HCN from methane with experimental demonstration of such event on laboratory base.
Here, we report the cyanide formation via oxidation of amino acids by geological available minerals. Using glycine as a representative amino acid substrate, we found that this reaction could take place under wide ranges of pH (2-13) and temperature (6 – 60 ℃). This oxidation reaction was monitored to reach equilibrium within 24 hours and the minimum amount of glycine required for cyanide generation could be decreased to 1 mM with a yield of 47%. Isotopic labeling experiment using UPLC-ESI-MS identified that cyanide was produced from 2-C position of glycine through a C-C bond cleavage pathway. And kinetic isotope experiment revealed that α-proton abstraction plays a crucial role in initiating this reaction. In addition to glycine, amino acid oxidation by natural mineral could be applied to all the 20 proteogenic amino acids and poly peptides of glycine. Product distribution varies with amino acids, but seven out of twenty amino acids have been identified to be active to generate cyanide. Ammonia and organic carboxylic acids appeared to be commonly produced from corresponding amino acids. Furthermore, intermediates of reductive Kreb’s Cycle (rTCA cycle), including pyruvate, oxaloacetate, keto-glutarate, succinate, fumarate, were detected from alanine, aspartate or glutamate.
The robustness of cyanide production from amino acids described here for the first time demonstrated a pathway independent of gaseous components of early atmosphere with detailed experimental investigation. It has been extensively studied that amino acids can be produced via multiple mechanisms and starting material throughout Earth history. Therefore, amino acids as alternative source of HCN offer great advantages due to the easy accessibility of diverse amino acid sources. We hope our discovery contributes to the current studies of prebiotic chemistry, especially HCN-based chemistry, by providing an efficient, robust and simple HCN generation pathway.