Ethanol represses the expression of methanol-inducible genes via acetyl-CoA synthesis in the yeast Komagataella phaffii
Ethanol represses the expression of methanol-inducible genes via acetyl-CoA synthesis in the yeast Komagataella phaffii
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DOI：
10.1038/s41598-018-36732-2
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发表时间：
2018-12-21
影响因子：
4.6
通讯作者：
Yurimoto, Hiroya
中科院分区：
文献类型：
--
作者：
Ohsawa, Shin;Nishida, Susumu;Yurimoto, Hiroya
在甲基营养型酵母中，即使在甲醇存在下，甲醇诱导基因的表达也会受到乙醇的抑制，这种现象称为乙醇抑制。研究了Komagataella phaffii（Pichia pastoris）乙醇阻遏的机理，发现乙醇通过乙醇脱氢酶、乙醛脱氢酶和乙酰辅酶A合成酶（ACS）的顺序反应合成乙酰辅酶A。ACS编码基因产物KpAcs 1的分子分析表明，其N-末端基序，这是保守的甲基营养型酵母，需要乙醇镇压。ACS活性在甲醇诱导的基因表达过程中下调，这部分依赖于自噬。此外，乙酰辅酶A的合成和磷酸化的转录因子KpMxr 1被发现有助于乙醇抑制的协同方式。
In methylotrophic yeasts, the expression of methanol-inducible genes is repressed by ethanol even in the presence of methanol, a phenomenon called ethanol repression. The mechanism of ethanol repression in Komagataella phaffii (Pichia pastoris) was studied, and acetyl-CoA synthesis from ethanol by sequential reactions of alcohol dehydrogenase, aldehyde dehydrogenase and acetyl-CoA synthetase (ACS) was involved in ethanol repression. Molecular analysis of the ACS-encoding gene product KpAcs1 revealed that its N-terminal motif, which is conserved in methylotrophic yeasts, was required for ethanol repression. ACS activity was downregulated during methanol-induced gene expression, which partially depended on autophagy. In addition, acetyl-CoA synthesis and phosphorylation of a transcription factor KpMxr1 were found to contribute to ethanol repression in a synergistic manner.