Furfural induces reactive oxygen species accumulation and cellular damage in Saccharomyces cerevisiae.
Furfural induces reactive oxygen species accumulation and cellular damage in Saccharomyces cerevisiae.
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DOI：
10.1186/1754-6834-3-2
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发表时间：
2010-01-15
影响因子：
6.3
通讯作者：
Gorsich SW
中科院分区：
文献类型：
--
作者：
Allen SA;Clark W;McCaffery JM;Cai Z;Lanctot A;Slininger PJ;Liu ZL;Gorsich SW
生物燃料为石油燃料提供了一种可行的替代品。然而，目前的方法是不够的，为了使用木质纤维素生物质作为发酵底物所需的技术面临着几个挑战。一个挑战是需要能够耐受木质纤维素发酵期间存在的抑制剂的稳健发酵微生物。这些抑制剂包括呋喃醛、糠醛，其在木质纤维素的弱酸预处理期间作为戊糖脱水的副产物释放。为了在糠醛的存在下生存，酵母细胞不仅需要将糠醛还原为毒性较小的呋喃甲醇，还需要保护自己并修复糠醛造成的任何损害。由于酵母中的糠醛耐受性需要功能性戊糖磷酸途径（PPP），并且PPP与活性氧（ROS）耐受性相关，因此我们决定研究糠醛是否诱导酵母中的ROS及其相关的细胞损伤。我们证明，糠醛诱导活性氧在酿酒酵母中的积累。此外，糠醛显示引起细胞损伤，这与细胞中ROS积累一致，包括对线粒体和空泡膜、肌动蛋白细胞骨架和核染色质的损伤。与阻止生长的糠醛浓度（50 mM）相比，当酵母在允许最终生长的糠醛浓度（25 mM）下生长时，糠醛诱导的损伤不太严重。这些数据表明，当酵母细胞遇到抑制剂糠醛时，它们不仅需要将糠醛还原为呋喃甲醇，而且还需要保护自己免受糠醛的细胞影响并修复所造成的任何损害。与50 mM糠醛相比，在25 mM糠醛下观察到的细胞损伤减少可能与以下观察结果有关：在25 mM糠醛下，酵母能够退出糠醛诱导的滞后期并恢复生长。了解糠醛的细胞效应将有助于指导未来的菌株开发，以工程菌株能够耐受或修复ROS和ROS的影响。
Biofuels offer a viable alternative to petroleum-based fuel. However, current methods are not sufficient and the technology required in order to use lignocellulosic biomass as a fermentation substrate faces several challenges. One challenge is the need for a robust fermentative microorganism that can tolerate the inhibitors present during lignocellulosic fermentation. These inhibitors include the furan aldehyde, furfural, which is released as a byproduct of pentose dehydration during the weak acid pretreatment of lignocellulose. In order to survive in the presence of furfural, yeast cells need not only to reduce furfural to the less toxic furan methanol, but also to protect themselves and repair any damage caused by the furfural. Since furfural tolerance in yeast requires a functional pentose phosphate pathway (PPP), and the PPP is associated with reactive oxygen species (ROS) tolerance, we decided to investigate whether or not furfural induces ROS and its related cellular damage in yeast. We demonstrated that furfural induces the accumulation of ROS in Saccharomyces cerevisiae. In addition, furfural was shown to cause cellular damage that is consistent with ROS accumulation in cells which includes damage to mitochondria and vacuole membranes, the actin cytoskeleton and nuclear chromatin. The furfural-induced damage is less severe when yeast are grown in a furfural concentration (25 mM) that allows for eventual growth after an extended lag compared to a concentration of furfural (50 mM) that prevents growth. These data suggest that when yeast cells encounter the inhibitor furfural, they not only need to reduce furfural into furan methanol but also to protect themselves from the cellular effects of furfural and repair any damage caused. The reduced cellular damage seen at 25 mM furfural compared to 50 mM furfural may be linked to the observation that at 25 mM furfural yeast were able to exit the furfural-induced lag phase and resume growth. Understanding the cellular effects of furfural will help direct future strain development to engineer strains capable of tolerating or remediating ROS and the effects of ROS.
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