title: Reconstruction and analysis of a genome-scale metabolic model of the oleaginous fungus Mortierella alpina.
abstract: BACKGROUND
  Mortierella alpina is an oleaginous fungus used in the industrial scale production of arachidonic acid (ARA). In order to investigate the metabolic characteristics at a systems level and to explore potential strategies for enhanced lipid production, a genome-scale metabolic model of M. alpina was reconstructed.
  
  
  RESULTS
  This model included 1106 genes, 1854 reactions and 1732 metabolites. On minimal growth medium, 86 genes were identified as essential, whereas 49 essential genes were identified on yeast extract medium. A series of sequential desaturase and elongase catalysed steps are involved in the synthesis of polyunsaturated fatty acids (PUFAs) from acetyl-CoA precursors, with concomitant NADPH consumption, and these steps were investigated in this study. Oxygen is known to affect the degree of unsaturation of PUFAs, and robustness analysis determined that an oxygen uptake rate of 2.0 mmol gDW(-1) h(-1) was optimal for ARA accumulation. The flux of 53 reactions involving NADPH was significantly altered at different ARA levels. Of these, malic enzyme (ME) was confirmed as a key component in ARA production and NADPH generation. When using minimization of metabolic adjustment, a knock-out of ME led to a 38.28% decrease in ARA production.
  
  
  CONCLUSIONS
  The simulation results confirmed the model as a useful tool for future research on the metabolism of PUFAs.
authors.affiliation: State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. ziye0911@gmail.com.|The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. ziye0911@gmail.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. nan1989111@gmail.com.|The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. nan1989111@gmail.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. haiqinchen@jiangnan.edu.cn.|Synergistic Innovation Center for Food Safety and Nutrition, School of Food Science and technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. haiqinchen@jiangnan.edu.cn.
authors.forename: Haiqin
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. yqchen@jiangnan.edu.cn.|Synergistic Innovation Center for Food Safety and Nutrition, School of Food Science and technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. yqchen@jiangnan.edu.cn.
authors.forename: Yong Q
authors.initials: YQ
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. weichen@jiangnan.edu.cn.|Synergistic Innovation Center for Food Safety and Nutrition, School of Food Science and technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. weichen@jiangnan.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. mingll@jiangnan.edu.cn.|The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. mingll@jiangnan.edu.cn.
authors.forename: Liming
authors.initials: L
authors.lastname: Liu
mesh_terms: D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis; D005285:Fermentation; D020043:Genes, Essential / Q000235:genetics; D016681:Genome, Fungal / Q000235:genetics; D023281:Genomics; D008954:Models, Biological; D020094:Mortierella / Q000235:genetics* / Q000378:metabolism*; D017421:Sequence Analysis
chemical_list: D005231:Fatty Acids, Unsaturated