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BMC Syst Biol. 2015 Jan 13;9:1. doi: 10.1186/s12918-014-0137-8.

Reconstruction and analysis of a genome-scale metabolic model of the oleaginous fungus Mortierella alpina.

Ye C1,2, Xu N3,4, Chen H5,6, Chen YQ7,8, Chen W9,10, Liu L11,12.

Author information

1
State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. ziye0911@gmail.com.
2
The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. ziye0911@gmail.com.
3
State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. nan1989111@gmail.com.
4
The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. nan1989111@gmail.com.
5
State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. haiqinchen@jiangnan.edu.cn.
6
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.
7
State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. yqchen@jiangnan.edu.cn.
8
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.
9
State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. weichen@jiangnan.edu.cn.
10
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.
11
State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. mingll@jiangnan.edu.cn.
12
The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. mingll@jiangnan.edu.cn.

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.

PMID:
25582171
PMCID:
PMC4301621
DOI:
10.1186/s12918-014-0137-8
[Indexed for MEDLINE]
Free PMC Article

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