Transcription factor Hap5 induces gsh2 expression to enhance 2-phenylethanol tolerance and production in an industrial yeast Candida glycerinogenes
Transcription factor Hap5 induces gsh2 expression to enhance 2-phenylethanol tolerance and production in an industrial yeast Candida glycerinogenes
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转录因子 Hap5 诱导 gsh2 表达，增强工业酵母产甘油假丝酵母的 2-苯乙醇耐受性和产量
DOI：
10.1007/s00253-020-10509-y
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发表时间：
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影响因子：
5
通讯作者：
bin zhuge
中科院分区：
文献类型：
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作者：
Yuqin wang;Zhongyuan zhang;xinyao lu;hong zong;bin zhuge
2-苯乙醇(2-PE)是一种重要的风味化合物，但也会严重影响细胞的生长，进而阻碍其生物合成。然而，2-PE耐受的分子机制尚不清楚。在本研究中，我们选择了一株耐2-PE胁迫的高产酵母--产甘油假丝酵母来揭示其耐受2-PE的机制。我们发现，Hap5是2-PE抗性的重要调节因子，2-PE胁迫对Hap5的诱导作用发生在转录后水平，而不是转录水平。在2-PE胁迫下，Hap5被激活并迅速进入细胞核。然后，核Hap5通过CCAAT box与谷胱甘肽合成酶(Gsh2)启动子结合，诱导Gsh2基因的表达。Gsh2表达的增加有助于提高细胞内谷胱甘肽的含量，从而减轻2-PE毒性引起的ROS积累、脂质过氧化和细胞膜损伤。具体地说，增加gsh2的表达不仅有效地提高了2-PE的耐受性(在29 mm2-PE下增加了33.7%的生物量)，而且还提高了2-PE的产量(提高了16.2%)。本研究扩大了我们对2-PE耐受机制的认识，也为提高2-PE的产量提供了一种有前景的策略。
2-Phenylethanol (2-PE) is an important flavor compound but also impairs cell growth severely, which in turn blocks its bioproduction. However, the molecular mechanism of 2-PE tolerance is unclear. In this study, a superb 2-PE stress-tolerant and producing yeast,Candida glycerinogenes, was selected to uncover the underlying mechanism of 2-PE tolerance. We discovered that Hap5 is an essential regulator to 2-PE resistance, and its induction by 2-PE stress occurs at the post-transcriptional level, rather than at the transcriptional level. Under 2-PE stress, Hap5 is activated and imported into the nucleus rapidly. Then, the nuclear Hap5 binds to the glutathione synthetase (gsh2) promoter via CCAAT box, to induce the expression ofgsh2gene. The increasedgsh2expression contributes to enhanced cellular glutathione content, and consequently alleviates ROS accumulation, lipid peroxidation, and cell membrane damage caused by 2-PE toxicity. Specifically, increasing the expression ofgsh2is effective in improving not just 2-PE tolerance (33.7% higher biomass under 29 mM 2-PE), but also 2-PE production (16.2% higher). This study extends our knowledge of 2-PE tolerance mechanism and also provides a promising strategy to improve 2-PE production.