Clostridium acetobutylicum and Clostridium ljungdahlii grown in a syntrophic culture were recently shown to fuse membranes and exchange cytosolic contents, yielding hybrid cells with significant shifts in gene expression and growth phenotypes. Here, we introduce a dynamic genome-scale metabolic modeling framework to explore how cell fusion alters the growth phenotype and panel of metabolites produced by this binary community. Computational results indicate C. ljungdahlii persists in the coculture through proteome exchange during fusing events, which endow C. ljungdahlii cells with expanded substrate utilization, and access to additional reducing equivalents from C. acetobutylicum-evolved H₂ and through acquisition of C. acetobutylicum-native cofactor-reducing enzymes. Simulations predict maximum theoretical ethanol and isopropanol yields that are increased by 0.64 mmol and 0.39 mmol per mmol hexose sugar consumed, respectively, during exponential growth when cell fusion is active. This modeling effort provides a mechanistic explanation for the metabolic outcome of cellular fusion and altered homeostasis achieved in this syntrophic clostridial community.

中文翻译：

---

丙酮丁醇梭菌/杨氏梭菌合成共培养的生长动力学、种间细胞融合和代谢建模

最近显示在同养培养中生长的丙酮丁醇梭菌和杨氏梭菌融合膜并交换细胞质内容物，产生基因表达和生长表型发生显着变化的杂交细胞。在这里，我们引入了一个动态的基因组规模代谢建模框架，以探索细胞融合如何改变由这个二元群落产生的生长表型和代谢物组。计算结果表明C. ljungdahlii在融合事件期间通过蛋白质组交换持续共培养，这使C. ljungdahlii细胞具有扩大的底物利用率，并获得来自C. acetobutylicum进化的 H _{2 的}额外还原当量并通过获得丙酮丁醇梭菌 -天然辅因子还原酶。模拟预测最大理论乙醇和异丙醇产量在细胞融合活跃时的指数生长期间，每消耗 mmol 己糖分别增加 0.64 mmol 和 0.39 mmol。这种建模工作为在这个同养梭菌群落中实现的细胞融合和改变的体内平衡的代谢结果提供了机械解释。