Shahreen Nabia, Ahn Jongsam, Alsiyabi Adil, Chowdhury Niaz B, Shinde Dhananjay, Chaudhari Sujata S, Bayles Kenneth W, Thomas Vinai Chittezham, Saha Rajib
University of Nebraska-Lincoln.
University of Nebraska Medical Center.
bioRxiv. 2024 Oct 18:2024.10.16.618751. doi: 10.1101/2024.10.16.618751.
During aerobic growth, relies on acetate overflow metabolism, a process where glucose is incompletely oxidized to acetate, for its bioenergetic needs. Acetate is not immediately captured as a carbon source and is excreted as waste by cells. The underlying factors governing acetate overflow in have not been identified. Here, we show that acetate overflow is favored due to a thermodynamic bottleneck in the TCA cycle, specifically involving the oxidation of succinate to fumarate by succinate dehydrogenase. This bottleneck reduces flux through the TCA cycle, making it more efficient for to generate ATP via acetate overflow metabolism. Additionally, the protein allocation cost of maintaining ATP flux through the restricted TCA cycle is greater than that of acetate overflow metabolism. Finally, we show that the TCA cycle bottleneck provides the flexibility to redirect carbon towards maintaining redox balance through lactate overflow when oxygen becomes limiting, albeit at the expense of ATP production through acetate overflow. Overall, our findings suggest that overflow metabolism offers distinct bioenergetic advantages over a thermodynamically constrained TCA cycle, potentially supporting its commensal-pathogen lifestyle.
在有氧生长过程中，[具体微生物名称未给出]依靠乙酸溢流代谢来满足其生物能量需求，这是一个葡萄糖不完全氧化为乙酸的过程。乙酸不会立即被捕获作为碳源，而是被细胞作为废物排出。尚未确定控制[具体微生物名称未给出]中乙酸溢流的潜在因素。在此，我们表明，由于三羧酸循环（TCA循环）中的一个热力学瓶颈，乙酸溢流受到青睐，具体涉及琥珀酸脱氢酶将琥珀酸氧化为延胡索酸。这个瓶颈降低了通过TCA循环的通量，使得[具体微生物名称未给出]通过乙酸溢流代谢产生ATP更有效。此外，通过受限的TCA循环维持ATP通量的蛋白质分配成本高于乙酸溢流代谢。最后，我们表明，当氧气变得有限时，TCA循环瓶颈为[具体微生物名称未给出]提供了灵活性，使其能够通过乳酸溢流将碳重新导向维持氧化还原平衡，尽管这是以通过乙酸溢流产生ATP为代价的。总体而言，我们的研究结果表明，溢流代谢相对于热力学受限的TCA循环具有明显的生物能量优势，这可能支持其共生病原体的生活方式。
