<b>Regulating the Metabolic Flux of Pyruvate Dehydrogenase Bypass to Enhance Lipid Production in </b><b><i>Saccharomyces cerevisiae</i></b>

To achieve high efficiency in microbial cell factories, it is crucial to redesign central carbon fluxes to ensure an adequate supply of precursors for producing high-value compounds. In this study, we employed a multi-omics approach to rearrange the central carbon flux of the pyruvate dehydrogenase (PDH) bypass, thereby enhancing the supply of intermediate precursors, specifically acetyl-CoA. This enhancement aimed to improve the biosynthesis of acetyl-CoA-derived compounds, such as terpenoids and fatty acid-derived molecules, in <i>Saccharomyces cerevisiae</i>. Through transcriptomic and lipidomic analyses, we identified <i>ALD4</i> as a key regulatory gene influencing lipid metabolism. Genetic validation demonstrated that overexpression of the mitochondrial acetaldehyde dehydrogenase (ALDH) gene <i>ALD4</i> resulted in a 20.1% increase in lipid production. This study provides theoretical support for optimising the performance of <i>S. cerevisiae</i> as a "cell factory" for the production of commercial compounds.This study aimed to identify a metabolic engineering strategy that increases lipid synthesis by<i> </i><i>S. cerevisiae</i> during anaerobic fermentation. Multi-omics analyses are conducted to identify important regulatory genes that responsible for increasing lipid synthesis. The synthesis of acetyl-CoA and lipids was effectively promoted by regulating the flow of glycolytic carbon flux to PDH bypass pathway. Our study provides new insights and directions for further development of PDH bypass-based metabolic engineering strategies to enhance the microbial synthesis of industrial lipid compounds.<br>

为实现微生物细胞工厂的高效运转，重新设计中心碳代谢流以保障高价值化合物合成所需前体的充足供给至关重要。本研究采用多组学方法，对丙酮酸脱氢酶（pyruvate dehydrogenase, PDH）旁路的中心碳代谢流进行重排，以此提升中间前体物质——尤其是乙酰辅酶A（acetyl-CoA）——的供应水平，旨在优化酿酒酵母（Saccharomyces cerevisiae）中乙酰辅酶A衍生化合物（如萜类及脂肪酸衍生分子）的生物合成。通过转录组学与脂质组学分析，我们鉴定出ALD4为影响脂质代谢的关键调控基因。遗传学验证实验表明，过表达线粒体乙醛脱氢酶（acetaldehyde dehydrogenase, ALDH）基因ALD4可使脂质产量提升20.1%。本研究为优化酿酒酵母作为商业化化合物生产"细胞工厂"的性能提供了理论支撑。本研究旨在开发可提升酿酒酵母厌氧发酵过程中脂质合成能力的代谢工程策略。通过多组学分析鉴定得到影响脂质合成的关键调控基因，调控糖酵解碳流向丙酮酸脱氢酶旁路的代谢流后，可有效促进乙酰辅酶A与脂质的合成。本研究为进一步开发基于丙酮酸脱氢酶旁路的代谢工程策略、强化工业脂质化合物的微生物合成提供了新的思路与方向。

搜集汇总

背景与挑战

背景概述

该数据集提供了一项关于调控酿酒酵母丙酮酸脱氢酶旁路代谢通量以增强脂质生产的研究原始数据。研究通过多组学分析识别出关键调控基因ALD4，其过表达可使脂质产量提高20.1%，为优化酿酒酵母作为'细胞工厂'生产工业脂质化合物提供了理论和数据支持。数据集包含Excel格式的图表原始文件，聚焦于代谢工程和脂质合成领域。