High-level production of nervonic acid in the oleaginous yeast Yarrowia lipolytica by systematic metabolic engineering

被引：11

作者：

Su H. ^{[1
,2
]}

Shi P. ^{[1
,3
]}

Shen Z. ^{[1
,3
]}

Meng H. ^{[1
,7
]}

Meng Z. ^{[1
,2
]}

Han X. ^{[1
]}

Chen Y. ^{[4
]}

Fan W. ^{[4
]}

Fa Y. ^{[1
,3
,5
]}

Yang C. ^{[6
]}

Li F. ^{[1
,3
,5
]}

Wang S. ^{[1
,3
,5
]}

机构：

[1] Key Laboratory of Biofuels, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao

[2] University of Chinese Academy of Sciences, Beijing

[3] Shandong Energy Institute, Qingdao

[4] Zhejiang Zhenyuan Biotech Co., LTD, Shaoxing

[5] Qingdao New Energy Shandong Laboratory, Qingdao

[6] State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao

[7] Qingdao Institute for Food and Drug Control, Qingdao

来源：

Communications Biology | / 6卷 / 1期

关键词：

D O I：

10.1038/s42003-023-05502-w

中图分类号：

学科分类号：

摘要：

Nervonic acid benefits the treatment of neurological diseases and the health of brain. In this study, we employed the oleaginous yeast Yarrowia lipolytica to overproduce nervonic acid oil by systematic metabolic engineering. First, the production of nervonic acid was dramatically improved by iterative expression of the genes ecoding β-ketoacyl-CoA synthase CgKCS, fatty acid elongase gELOVL6 and desaturase MaOLE2. Second, the biosynthesis of both nervonic acid and lipids were further enhanced by expression of glycerol-3-phosphate acyltransferases and diacylglycerol acyltransferases from Malania oleifera in endoplasmic reticulum (ER). Third, overexpression of a newly identified ER structure regulator gene YlINO2 led to a 39.3% increase in lipid production. Fourth, disruption of the AMP-activated S/T protein kinase gene SNF1 increased the ratio of nervonic acid to lignoceric acid by 61.6%. Next, pilot-scale fermentation using the strain YLNA9 exhibited a lipid titer of 96.7 g/L and a nervonic acid titer of 17.3 g/L (17.9% of total fatty acids), the highest reported titer to date. Finally, a proof-of-concept purification and separation of nervonic acid were performed and the purity of it reached 98.7%. This study suggested that oleaginous yeasts are attractive hosts for the cost-efficient production of nervonic acid and possibly other very long-chain fatty acids (VLCFAs). © 2023, The Author(s).

引用

共 86 条

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