TY - JOUR
T1 - Engineering oxidative stress defense pathways to build a robust lipid production platform in Yarrowia lipolytica
AU - Xu, Peng
AU - Qiao, Kangjian
AU - Stephanopoulos, Gregory
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/7
Y1 - 2017/7
N2 - 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.
AB - 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.
KW - Yarrowia lipolytica
KW - aldehyde detoxification
KW - fungal morphology
KW - lipogenic pathway
KW - metabolic engineering
KW - oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=85018602315&partnerID=8YFLogxK
U2 - 10.1002/bit.26285
DO - 10.1002/bit.26285
M3 - 文章
C2 - 28295166
AN - SCOPUS:85018602315
SN - 0006-3592
VL - 114
SP - 1521
EP - 1530
JO - Biotechnology and Bioengineering
JF - Biotechnology and Bioengineering
IS - 7
ER -