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在酿酒酵母中通过删除转录因子基因 ino2/ino4 来实现脂质代谢的全局重布线以产生类胡萝卜素。

Global rewiring of lipid metabolism to produce carotenoid by deleting the transcription factor genes ino2/ino4 in Saccharomyces cerevisiae.

机构信息

Key Laboratory of Agricultural Microbiomics and Precision Application (MARA), Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Key Laboratory of Agricultural Microbiome (MARA), State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, People's Republic of China.

Key Laboratory of Agricultural Microbiomics and Precision Application (MARA), Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Key Laboratory of Agricultural Microbiome (MARA), State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, People's Republic of China.

出版信息

Int J Biol Macromol. 2024 Apr;264(Pt 1):130400. doi: 10.1016/j.ijbiomac.2024.130400. Epub 2024 Feb 25.

DOI:10.1016/j.ijbiomac.2024.130400
PMID:38412934
Abstract

The transcription factor complex INO2 and INO4 in Saccharomyces cerevisiae plays a vital role in lipid biosynthesis by activating multiple genes in the biosynthetic pathways of phospholipid, fatty acid, and sterol. Previous studies have reported conflicting results regarding the effects of ino2 and ino4 gene expression levels on target chemicals. Therefore, this study aimed to examine the influence of different ino2 and ino4 expression levels on carotenoid production (e.g., lycopene), which shares a common precursor, acetyl-CoA, with lipid metabolism. Surprisingly, 2.6- and 1.8-fold increase in lycopene yield in the ino2 and ino4 deletion strains were found, respectively. In contrast, ino2 overexpression did not promote lycopene accumulation. Additionally, there was a decrease in intracellular free fatty acids in the ino2 deletion strain. Comparative transcriptome analysis revealed a significant downregulation of genes related to lipid biosynthesis in the ino2 deletion strain. To our knowledge, this is the first report showing that deletion of transcription factor genes ino2 and ino4 can facilitate lycopene accumulation. These findings hold significant implications for the development of metabolically engineered S. cerevisiae with enhanced carotenoid production.

摘要

酿酒酵母中的转录因子复合物 INO2 和 INO4 通过激活磷脂、脂肪酸和固醇生物合成途径中的多个基因,在脂质生物合成中发挥着至关重要的作用。先前的研究报告称,INO2 和 INO4 基因表达水平对目标化学物质的影响存在矛盾。因此,本研究旨在研究不同 INO2 和 INO4 表达水平对类胡萝卜素(如番茄红素)产生的影响,因为类胡萝卜素与脂质代谢共享一个共同的前体乙酰辅酶 A。令人惊讶的是,INO2 和 INO4 缺失菌株中的番茄红素产量分别增加了 2.6 倍和 1.8 倍。相比之下,INO2 的过表达并没有促进番茄红素的积累。此外,INO2 缺失菌株中的细胞内游离脂肪酸减少。比较转录组分析显示,INO2 缺失菌株中与脂质生物合成相关的基因显著下调。据我们所知,这是首次报道转录因子基因 INO2 和 INO4 的缺失可以促进番茄红素的积累。这些发现对开发具有增强类胡萝卜素生产能力的代谢工程酿酒酵母具有重要意义。

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1
Global rewiring of lipid metabolism to produce carotenoid by deleting the transcription factor genes ino2/ino4 in Saccharomyces cerevisiae.在酿酒酵母中通过删除转录因子基因 ino2/ino4 来实现脂质代谢的全局重布线以产生类胡萝卜素。
Int J Biol Macromol. 2024 Apr;264(Pt 1):130400. doi: 10.1016/j.ijbiomac.2024.130400. Epub 2024 Feb 25.
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Autoregulated expression of the yeast INO2 and INO4 helix-loop-helix activator genes effects cooperative regulation on their target genes.酵母INO2和INO4螺旋-环-螺旋激活基因的自动调节表达对其靶基因产生协同调节作用。
Mol Cell Biol. 1995 Mar;15(3):1709-15. doi: 10.1128/MCB.15.3.1709.
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Integrated analysis, transcriptome-lipidome, reveals the effects of INO-level (INO2 and INO4) on lipid metabolism in yeast.整合分析,转录组-脂质组,揭示了INO水平(INO2和INO4)对酵母脂质代谢的影响。
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Dimerization of yeast transcription factors Ino2 and Ino4 is regulated by precursors of phospholipid biosynthesis mediated by Opi1 repressor.酵母转录因子Ino2和Ino4的二聚化受由Opi1阻遏物介导的磷脂生物合成前体的调控。
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Ribosomal protein genes in the yeast Candida albicans may be activated by a heterodimeric transcription factor related to Ino2 and Ino4 from S. cerevisiae.白色念珠菌中的核糖体蛋白基因可能由一种与酿酒酵母的Ino2和Ino4相关的异源二聚体转录因子激活。
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Influence of gene dosage and autoregulation of the regulatory genes INO2 and INO4 on inositol/choline-repressible gene transcription in the yeast Saccharomyces cerevisiae.基因剂量以及调控基因INO2和INO4的自动调节对酿酒酵母中肌醇/胆碱可抑制基因转录的影响。
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Transcription of INO2 and INO4 is regulated by the state of protein N-myristoylation in Saccharomyces cerevisiae.酿酒酵母中INO2和INO4的转录受蛋白质N-肉豆蔻酰化状态的调控。
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TFIIB and subunits of the SAGA complex are involved in transcriptional activation of phospholipid biosynthetic genes by the regulatory protein Ino2 in the yeast Saccharomyces cerevisiae.在酿酒酵母中,TFIIB和SAGA复合物的亚基参与了调控蛋白Ino2对磷脂生物合成基因的转录激活。
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INO1-100: an allele of the Saccharomyces cerevisiae INO1 gene that is transcribed without the action of the positive factors encoded by the INO2, INO4, SWI1, SWI2 and SWI3 genes.INO1 - 100:酿酒酵母INO1基因的一个等位基因,其转录无需INO2、INO4、SWI1、SWI2和SWI3基因所编码的正向因子的作用。
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Overproduction of the Opi1 repressor inhibits transcriptional activation of structural genes required for phospholipid biosynthesis in the yeast Saccharomyces cerevisiae.在酿酒酵母中,Opi1阻遏蛋白的过量产生会抑制磷脂生物合成所需结构基因的转录激活。
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