It has recently been shown that in anaerobic microorganisms the tricarboxylic acid (TCA) cycle, including the seemingly irreversible citrate synthase reaction, can be reversed and used for autotrophic fixation of carbon^1,2. This reversed oxidative TCA cycle requires ferredoxin-dependent 2-oxoglutarate synthase instead of the NAD-dependent dehydrogenase as well as extremely high levels of citrate synthase (more than 7% of the proteins in the cell). In this pathway, citrate synthase replaces ATP-citrate lyase of the reductive TCA cycle, which leads to the spending of one ATP-equivalent less per one turn of the cycle. Here we show, using the thermophilic sulfur-reducing deltaproteobacterium Hippea maritima, that this route is driven by high partial pressures of CO₂. These high partial pressures are especially important for the removal of the product acetyl coenzyme A (acetyl-CoA) through reductive carboxylation to pyruvate, which is catalysed by pyruvate synthase. The reversed oxidative TCA cycle may have been functioning in autotrophic CO₂ fixation in a primordial atmosphere that is assumed to have been rich in CO₂.

最近表明，在厌氧微生物中，三羧酸 (TCA) 循环，包括看似不可逆的柠檬酸合酶反应，可以逆转并用于碳^1,2的自养固定。这种逆转的氧化 TCA 循环需要依赖铁氧还蛋白的 2-氧代戊二酸合酶而不是依赖 NAD 的脱氢酶以及极高水平的柠檬酸合酶（超过细胞中 7% 的蛋白质）。在此途径中，柠檬酸合酶取代了还原性 TCA 循环的 ATP-柠檬酸裂解酶，这导致每循环一圈消耗一个 ATP-当量。在这里，我们使用嗜热硫还原 deltaproteobacterium Hippea maritima表明，这条路线是由 CO ₂的高分压驱动的. 这些高分压对于通过还原羧化生成丙酮酸（由丙酮酸合酶催化）去除产物乙酰辅酶 A（乙酰辅酶 A）尤为重要。在假定富含 CO ₂的原始大气中，逆向氧化 TCA 循环可能在自养 CO ₂固定中发挥作用。