Engineering oxidative stress defense pathways to build a robust lipid production platform in Yarrowia lipolytica

Xu, Peng; Qiao, Kangjian; Stephanopoulos, Gregory

doi:10.1002/bit.26285

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

Journal Article · Tue Apr 18 00:00:00 EDT 2017 · Biotechnology and Bioengineering

DOI:https://doi.org/10.1002/bit.26285· OSTI ID:1401898

^[1]; Qiao, Kangjian ^[2]; Stephanopoulos, Gregory ^[2]

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
Department of Chemical Engineering Massachusetts Institute of Technology Cambridge Massachusetts 02139

ABSTRACT Microbially derived lipids have recently attracted renewed interests due to their broad applications in production of green diesels, cosmetic additives, and oleochemicals. Metabolic engineering efforts have targeted a large portfolio of biosynthetic pathways to efficiently convert sugar to lipids in oleaginous yeast. In the engineered overproducing strains, endogenous cell metabolism typically generates harmful electrophilic molecules that compromise cell fitness and productivity. Lipids, particularly unsaturated fatty acids, are highly susceptible to oxygen radical attack and the resulting oxidative species are detrimental to cell metabolism and limit lipid productivity. In this study, we investigated cellular oxidative stress defense pathways in Yarrowia lipolytica to further improve the lipid titer, yield, and productivity. Specifically, we determined that coupling glutathione disulfide reductase and glucose‐6‐phosphate dehydrogenase along with aldehyde dehydrogenase are efficient solutions to combat reactive oxygen and aldehyde stress in Y. lipolytica . With the reported engineering strategies, we were able to synchronize cell growth and lipid production, improve cell fitness and morphology, and achieved industrially‐relevant level of lipid titer (72.7 g/L), oil content (81.4%) and productivity (0.97 g/L/h) in controlled bench‐top bioreactors. The strategies reported here represent viable steps in the development of sustainable biorefinery platforms that potentially upgrade low value carbons to high value oleochemicals and biofuels. Biotechnol. Bioeng. 2017;114: 1521–1530. © 2017 Wiley Periodicals, Inc.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: DE‐SC0008744

OSTI ID:: 1401898

Journal Information:: Biotechnology and Bioengineering, Journal Name: Biotechnology and Bioengineering Vol. 114 Journal Issue: 7; ISSN 0006-3592

Publisher:: Wiley Blackwell (John Wiley & Sons)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 115 works

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