Increased accumulation of fatty acids in engineered Saccharomyces cerevisiae by co-overexpression of interorganelle tethering protein and lipases

IF 4.5 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

New biotechnology Pub Date : 2024-11-28 DOI:10.1016/j.nbt.2024.11.005

Guoli Wang , Mingkai Li , Mengyu Ma , Zhenke Wu, Xiqin Liang, Qiusheng Zheng, Defang Li, Tianyue An

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引用次数: 0

Abstract

Fatty acids (FAs) and their derivatives are versatile chemicals widely used in various industries. Synthetic biology, using microbial cell factories, emerges as a promising alternative technology for FA production. To enhance the production capacity of these microbial chassis, additional engineering strategies are imperative. Based on the comparison of the morphological changes of lipid droplets (LDs) between oleaginous and non-oleaginous yeasts, we developed a new engineering strategy to increase the accumulation of FAs in Saccharomyces cerevisiae through manipulation of regulation factor and lipases related to LD. The increased biogenesis of LDs, achieved by overexpressing the interorganelle tethering protein Mdm1, coupled with the accelerated degradation of LDs through upregulated lipases, resulted in a 10.70-fold increase in total FAs production. Co-overexpression of Mdm1 and selected lipases significantly improved the biosynthesis of FAs and linoleic acid in the engineered S. cerevisiae. The efficient LD-based metabolic engineering strategy presented in this study holds the potential to advance the high-level production of FAs and their derivatives in microbial cell factories.

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通过细胞器间栓系蛋白和脂肪酶的共同过表达，增加了工程酿酒酵母中脂肪酸的积累

脂肪酸及其衍生物是广泛应用于各个工业领域的通用化学品。合成生物学，利用微生物细胞工厂，出现了一个有前途的替代技术的FA生产。为了提高这些微生物底盘的生产能力，额外的工程策略是必不可少的。在比较产油酵母和非产油酵母的脂滴形态变化的基础上，我们开发了一种新的工程策略，通过操纵与脂滴相关的调节因子和脂肪酶来增加酿酒酵母中FAs的积累。脂滴的增加是通过过表达细胞器间系聚蛋白Mdm1来实现的，同时通过上调脂肪酶来加速脂滴的降解。导致总FAs产量增加10.70倍。共同过表达Mdm1和选定的脂肪酶显著提高了工程酿酒酵母中FAs和亚油酸的生物合成。本研究提出的高效的基于ld的代谢工程策略有可能促进微生物细胞工厂中FAs及其衍生物的高水平生产。

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来源期刊

New biotechnology 生物-生化研究方法

CiteScore

11.40

自引率

1.90%

发文量

审稿时长

1 months

期刊介绍： New Biotechnology is the official journal of the European Federation of Biotechnology (EFB) and is published bimonthly. It covers both the science of biotechnology and its surrounding political, business and financial milieu. The journal publishes peer-reviewed basic research papers, authoritative reviews, feature articles and opinions in all areas of biotechnology. It reflects the full diversity of current biotechnology science, particularly those advances in research and practice that open opportunities for exploitation of knowledge, commercially or otherwise, together with news, discussion and comment on broader issues of general interest and concern. The outlook is fully international. The scope of the journal includes the research, industrial and commercial aspects of biotechnology, in areas such as: Healthcare and Pharmaceuticals; Food and Agriculture; Biofuels; Genetic Engineering and Molecular Biology; Genomics and Synthetic Biology; Nanotechnology; Environment and Biodiversity; Biocatalysis; Bioremediation; Process engineering.