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首页> 美国卫生研究院文献>PLoS Clinical Trials >Investigate the Metabolic Reprogramming of Saccharomyces cerevisiae for Enhanced Resistance to Mixed Fermentation Inhibitors via 13C Metabolic Flux Analysis
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Investigate the Metabolic Reprogramming of Saccharomyces cerevisiae for Enhanced Resistance to Mixed Fermentation Inhibitors via 13C Metabolic Flux Analysis

机译：通过13C代谢通量分析研究酿酒酵母的代谢重编程以增强对混合发酵抑制剂的抗性

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The fermentation inhibitors from the pretreatment of lignocellulosic materials, e.g., acetic acid and furfural, are notorious due to their negative effects on the cell growth and chemical production. However, the metabolic reprogramming of the cells under these stress conditions, especially metabolic response for resistance to mixed inhibitors, has not been systematically investigated and remains mysterious. Therefore, in this study, 13C metabolic flux analysis (13C-MFA), a powerful tool to elucidate the intracellular carbon flux distributions, has been applied to two Saccharomyces cerevisiae strains with different tolerances to the inhibitors under acetic acid, furfural, and mixed (i.e., acetic acid and furfural) stress conditions to unravel the key metabolic responses. By analyzing the intracellular carbon fluxes as well as the energy and cofactor utilization under different conditions, we uncovered varied metabolic responses to different inhibitors. Under acetate stress, ATP and NADH production was slightly impaired, while NADPH tended towards overproduction. Under furfural stress, ATP and cofactors (including both NADH and NADPH) tended to be overproduced. However, under dual-stress condition, production of ATP and cofactors was severely impaired due to synergistic stress caused by the simultaneous addition of two fermentation inhibitors. Such phenomenon indicated the pivotal role of the energy and cofactor utilization in resisting the mixed inhibitors of acetic acid and furfural. Based on the discoveries, valuable insights are provided to improve the tolerance of S. cerevisiae strain and further enhance lignocellulosic fermentation.
机译：来自木质纤维素材料例如乙酸和糠醛的预处理的发酵抑制剂由于其对细胞生长和化学产生的负面影响而臭名昭著。然而，在这些应激条件下细胞的代谢重编程，特别是对混合抑制剂的抗性的代谢反应，尚未得到系统的研究，仍然是一个谜。因此，在这项研究中， 13 C代谢通量分析（ 13 C-MFA），一种阐明细胞内碳通量分布的有力工具，已应用于两种酿酒酵母菌株在乙酸，糠醛和混合（即乙酸和糠醛）胁迫条件下对抑制剂的耐受性不同，以揭示关键的代谢反应。通过分析细胞内的碳通量以及在不同条件下的能量和辅因子利用，我们发现了对不同抑制剂的不同代谢反应。在乙酸盐胁迫下，ATP和NADH的生产受到轻微损害，而NADPH则趋向于生产过剩。在糠醛胁迫下，ATP和辅助因子（包括NADH和NADPH）都倾向于过量生产。然而，在双重胁迫条件下，由于同时添加两种发酵抑制剂引起的协同胁迫，ATP和辅因子的生产受到严重损害。这种现象表明能量和辅助因子利用在抵抗乙酸和糠醛的混合抑制剂中起关键作用。基于这些发现，提供了有价值的见解，以提高酿酒酵母菌株的耐受性并进一步增强木质纤维素发酵。

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