文献类型：期刊文献

英文题名：Remodeling the Homologous Recombination Mechanism of Yarrowia lipolytica for High-Level Biosynthesis of Squalene

作者：Xu, Man[1];Yang, Nan[1];Pan, Jiang[1];Hua, Qiang[1];Li, Chun-Xiu[1];Xu, Jian-He[1]

机构：[1]East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg, Sch Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2024

卷号：72

期号：17

起止页码：9984

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20241715971129);WOS:【SCI-EXPANDED(收录号:WOS:001240894000001)】；

基金：This work was financially supported by the National Key Research and Development Program of China (2019YFA0905000), the National Natural Science Foundation of China (21871085 and 31971380), and the Fundamental Research Funds for the Central Universities (222201714026).

语种：英文

外文关键词：homologous recombination; squalene; Yarrowia lipolytica; metabolic engineering; acetyl coenzyme A

摘要：Squalene is a high-value antioxidant with many commercial applications. The use of microbial cell factories to produce squalene as an alternative to plant and animal extracts could meet increasing market demand. Yarrowia lipolytica is an excellent host for squalene production due to its high levels of acetyl-CoA and a hydrophobic environment. However, the need for precise and complicated gene editing has hindered the industrialization of this strain. Herein, the rapid construction of a strain with high squalene production was achieved by enhancing the homologous recombination efficiency in Y. lipolytica. First, remodeling of the homologous recombination efficiency resulted in a 10-fold increase in the homologous recombination rate. Next, the whole mevalonate pathway was integrated into the chromosome to enhance squalene production. Then, a higher level of squalene accumulation was achieved by increasing the level of acetyl coenzyme A and regulating the downstream steroid synthesis pathway. Finally, the squalene production reached 35 g/L after optimizing the fermentation conditions and performing a fed-batch culture in a 5 L jar fermenter. This is the highest squalene production ever reported to date by de novo biosynthesis without adding any inhibitors, paving a new path toward the industrial production of squalene and its downstream products.