skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Engineering oxidative stress defense pathways to build a robust lipid production platform in Yarrowia lipolytica: Engineering robust microbial oil cell factory

Authors:
ORCiD logo [1];  [2];  [2]
  1. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge Massachusetts 02139, Department of Chemical, Biochemical and Environmental Engineering, University of Maryland, Baltimore County, Baltimore Maryland
  2. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge Massachusetts 02139
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1401898
Grant/Contract Number:
SC0008744
Resource Type:
Journal Article: Publisher's Accepted Manuscript
Journal Name:
Biotechnology and Bioengineering
Additional Journal Information:
Journal Volume: 114; Journal Issue: 7; Related Information: CHORUS Timestamp: 2017-10-20 18:05:25; Journal ID: ISSN 0006-3592
Publisher:
Wiley Blackwell (John Wiley & Sons)
Country of Publication:
United States
Language:
English

Citation Formats

Xu, Peng, Qiao, Kangjian, and Stephanopoulos, Gregory. Engineering oxidative stress defense pathways to build a robust lipid production platform in Yarrowia lipolytica: Engineering robust microbial oil cell factory. United States: N. p., 2017. Web. doi:10.1002/bit.26285.
Xu, Peng, Qiao, Kangjian, & Stephanopoulos, Gregory. Engineering oxidative stress defense pathways to build a robust lipid production platform in Yarrowia lipolytica: Engineering robust microbial oil cell factory. United States. doi:10.1002/bit.26285.
Xu, Peng, Qiao, Kangjian, and Stephanopoulos, Gregory. Tue . "Engineering oxidative stress defense pathways to build a robust lipid production platform in Yarrowia lipolytica: Engineering robust microbial oil cell factory". United States. doi:10.1002/bit.26285.
@article{osti_1401898,
title = {Engineering oxidative stress defense pathways to build a robust lipid production platform in Yarrowia lipolytica: Engineering robust microbial oil cell factory},
author = {Xu, Peng and Qiao, Kangjian and Stephanopoulos, Gregory},
abstractNote = {},
doi = {10.1002/bit.26285},
journal = {Biotechnology and Bioengineering},
number = 7,
volume = 114,
place = {United States},
year = {Tue Apr 18 00:00:00 EDT 2017},
month = {Tue Apr 18 00:00:00 EDT 2017}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1002/bit.26285

Citation Metrics:
Cited by: 11works
Citation information provided by
Web of Science

Save / Share:
  • Cited by 55
  • Cited by 81
  • ABSTRACT The yeastYarrowia lipolyticais a potent accumulator of lipids, and lipogenesis in this organism can be influenced by a variety of factors, such as genetics and environmental conditions. Using a multifactorial study, we elucidated the effects of both genetic and environmental factors on regulation of lipogenesis inY. lipolyticaand identified how two opposite regulatory states both result in lipid accumulation. This study involved comparison of a strain overexpressing diacylglycerol acyltransferase (DGA1) with a control strain grown under either nitrogen or carbon limitation conditions. A strong correlation was observed between the responses on the transcript and protein levels. Combination ofDGA1overexpression with nitrogen limitationmore » resulted in a high level of lipid accumulation accompanied by downregulation of several amino acid biosynthetic pathways, including that of leucine in particular, and these changes were further correlated with a decrease in metabolic fluxes. This downregulation was supported by the measured decrease in the level of 2-isopropylmalate, an intermediate of leucine biosynthesis. Combining the multi-omics data with putative transcription factor binding motifs uncovered a contradictory role for TORC1 in controlling lipid accumulation, likely mediated through 2-isopropylmalate and a Leu3-like transcription factor. IMPORTANCEThe ubiquitous metabolism of lipids involves refined regulation, and an enriched understanding of this regulation would have wide implications. Various factors can influence lipid metabolism, including the environment and genetics. We demonstrated, using a multi-omics and multifactorial experimental setup, that multiple factors affect lipid accumulation in the yeastYarrowia lipolytica. Using integrative analysis, we identified novel interactions between nutrient restriction and genetic factors involving regulators that are highly conserved among eukaryotes. Given that lipid metabolism is involved in many diseases but is also vital to the development of microbial cell factories that can provide us with sustainable fuels and oleochemicals, we envision that our report introduces foundational work to further unravel the regulation of lipid accumulation in eukaryal cells.« less
  • Current biological pathways to produce biofuel intermediates amenable to separations and catalytic upgrading to hydrocarbon fuels are not cost effective. Previously, oleaginous yeasts have been investigated primarily for lipid production. However, yeasts store neutral lipids intracellularly making recovery difficult and expensive. In addition, once recovered from the cells, lipids are difficult to blend directly with the existing fuels without upgrading. We have, therefore, begun to investigate secreted fatty acid-derived products which can be easily recovered and upgraded to fuels. In this study, we successfully demonstrate the production of fatty alcohols by the oleaginous yeasts, Yarrowia lipolytica and Lipomyces starkeyi, throughmore » expression of the fatty acyl-CoA reductase gene from Marinobactor aquaeolei VT8. This strategy resulted in the production of 167 and 770 mg/L of fatty alcohols in shake flask from Y. lipolytica and L starkeyi, respectively. When using a dodecane overlay during fermentation, 92 and 99% of total fatty alcohols produced by Y. lipolytica and L. starkeyi, respectively, were extracted into the dodecane phase, which compares favorably to the 3 and 50% recovered, respectively, without the dodecane layer. In both oleaginous yeasts, long chain length, saturated fatty alcohols, i.e., hexadecanol (C16:0) and octadecanol (C18:0), were predominant and accounted for more than 85% of the total fatty alcohols produced. To the best of our knowledge, this is the first report of fatty alcohol production in L. starkeyi. Furthermore, this work demonstrates that the oleaginous yeasts, Y. lipolytica and L. starkeyi, can serve as platform organisms for the production of fatty acid-derived biofuels and bioproducts.« less