title: Metabolic Engineering of Mortierella alpina for Enhanced Arachidonic Acid Production through the NADPH-Supplying Strategy.
abstract: NADPH is known to be a key cofactor required for fatty acid synthesis and desaturation. Various enzymatic reactions can generate NADPH. To determine the effect of NADPH sources on lipogenesis, glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (PGD), isocitrate dehydrogenase (IDH), and malic enzyme (ME) were overexpressed in Mortierella alpina Our results showed that G6PD2 had the most significant effect on fatty acid synthesis, with a 1.7-fold increase in total fatty acid, whereas ME2 was more effective in desaturation, with a 1.5-fold increase in arachidonic acid (AA) content over control. Co-overexpression of G6PD2 and ME2 improved both fatty acid synthesis and desaturation. Within 96 h of fermentation using the fed-batch method, the co-overexpressing strain accumulated AA at a productivity of 1.9 ± 0.2 g/(liter · day), which was 7.2-fold higher than that in the M. alpina control that was cultured in a flask.
  
  
  
  This study proved that the pentose phosphate pathway is the major NADPH contributor during fatty acid synthesis in M. alpina The NADPH sources may be differently responsible for fatty acid synthesis or desaturation. Co-overexpression of G6PD2 and ME2 significantly increases AA production.
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, People's Republic of China.
authors.forename: Guangfei
authors.initials: G
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, People's Republic of China haiqinchen@jiangnan.edu.cn.|Synergistic Innovation Center for Food Safety and Nutrition, Wuxi, People's Republic of China.
authors.forename: Haiqin
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, People's Republic of China.|Synergistic Innovation Center for Food Safety and Nutrition, Wuxi, People's Republic of China.
authors.forename: Zhennan
authors.initials: Z
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, People's Republic of China.|Synergistic Innovation Center for Food Safety and Nutrition, Wuxi, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, People's Republic of China.|Synergistic Innovation Center for Food Safety and Nutrition, Wuxi, People's Republic of China.|Beijing Innovation Centre of Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, People's Republic of China.|Synergistic Innovation Center for Food Safety and Nutrition, Wuxi, People's Republic of China.|Departments of Cancer Biology and Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Yong Q
authors.initials: YQ
authors.lastname: Chen
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism*; D015870:Gene Expression; D060847:Metabolic Engineering / Q000379:methods*; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D020094:Mortierella / Q000235:genetics* / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*
chemical_list: D016718:Arachidonic Acid; D009249:NADP