NASA Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA, 91109, USA.
Department of Chemistry, California Institute of Technology, 1200 E. California Blvd, Pasadena, CA, 91125, USA.
Orig Life Evol Biosph. 2020 Jun;50(1-2):35-55. doi: 10.1007/s11084-019-09590-9. Epub 2020 Jan 25.
Understanding the emergence of metabolic pathways is key to unraveling the factors that promoted the origin of life. One popular view is that protein cofactors acted as catalysts prior to the evolution of the protein enzymes with which they are now associated. We investigated the stability of acetyl coenzyme A (Acetyl Co-A, the group transfer cofactor in citric acid synthesis in the TCA cycle) under early Earth conditions, as well as whether Acetyl Co-A or its small molecule analogs thioacetate or acetate can catalyze the transfer of an acetyl group onto oxaloacetate in the absence of the citrate synthase enzyme. Several different temperatures, pH ranges, and compositions of aqueous environments were tested to simulate the Earth's early ocean and its possible components; the effect of these variables on oxaloacetate and cofactor chemistry were assessed under ambient and anoxic conditions. The cofactors tested are chemically stable under early Earth conditions, but none of the three compounds (Acetyl Co-A, thioacetate, or acetate) promoted synthesis of citric acid from oxaloacetate under the conditions tested. Oxaloacetate reacted with itself and/or decomposed to form a sequence of other products under ambient conditions, and under anoxic conditions was more stable; under ambient conditions the specific chemical pathways observed depended on the environmental conditions such as pH and presence/absence of bicarbonate or salt ions in early Earth ocean simulants. This work demonstrates the stability of these metabolic intermediates under anoxic conditions. However, even though free cofactors may be stable in a geological environmental setting, an enzyme or other mechanism to promote reaction specificity would likely be necessary for at least this particular reaction to proceed.
理解代谢途径的出现是揭示促进生命起源的因素的关键。一种流行的观点是，在蛋白质酶出现之前，蛋白质辅因子就已经作为催化剂发挥作用了，而现在它们与这些酶结合在一起。我们研究了乙酰辅酶 A（Acetyl Co-A，柠檬酸合成中三羧酸循环的基团转移辅因子）在早期地球条件下的稳定性，以及在没有柠檬酸合酶的情况下，乙酰辅酶 A 或其小分子类似物硫代乙酸盐或乙酸盐是否可以催化乙酰基转移到草酰乙酸上。我们测试了几种不同的温度、pH 值范围和水相环境的组成，以模拟地球早期的海洋及其可能的成分；在有氧和无氧条件下，评估了这些变量对草酰乙酸和辅因子化学的影响。测试的辅因子在早期地球条件下化学稳定，但这三种化合物（乙酰辅酶 A、硫代乙酸盐或乙酸盐）都没有在测试条件下促进草酰乙酸合成柠檬酸。在有氧条件下，草酰乙酸与自身反应并/或分解形成一系列其他产物，而在无氧条件下则更稳定；在有氧条件下，观察到的特定化学途径取决于环境条件，如 pH 值以及早期地球海洋模拟物中是否存在碳酸氢盐或盐离子。这项工作表明这些代谢中间体在无氧条件下是稳定的。然而，即使游离辅因子在地质环境中稳定，至少对于这种特定反应，可能需要酶或其他机制来促进反应特异性。
