Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production

Ye, Chao; Qiao, Weihua; Yu, Xiaobin; Ji, Xiaojun; Huang, He; Collier, Jackie L.; Liu, Liming

doi:10.1186/s12864-015-2042-y

Title: Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production

Journal Article · 15 October 2015 · BMC Genomics

DOI: https://doi.org/10.1186/s12864-015-2042-y · OSTI ID:1626791

Ye, Chao ^[1]; Qiao, Weihua ^[2]; Yu, Xiaobin ^[3]; Ji, Xiaojun ^[4]; Huang, He ^[4]; Collier, Jackie L. ^[5]; Liu, Liming ^[6]

Jiangnan University (China). State Key Laboratory of Food Science and Technology; Jiangnan University (China). Ministry of Education. The Key Laboratory of Industrial Biotechnology.; DOE/OSTI
Jiangnan University (China). State Key Laboratory of Food Science and Technology; Jiangnan University (China). Ministry of Education. The Key Laboratory of Industrial Biotechnology.
Jiangnan University (China). Ministry of Education. The Key Laboratory of Industrial Biotechnology.
Nanjing Univ. of Technology (China). State Key Lab. of Materials-Oriented Chemical Engineering (MCE). College of Biotechnology and Pharmaceutical Engineering
Stony Brook Univ., NY (United States). School of Marine and Atmospheric Sciences
Jiangnan University (China). State Key Laboratory of Food Science and Technology; Jiangnan University (China). Ministry of Education. The Key Laboratory of Industrial Biotechnology.

Schizochytrium limacinum SR21 is a potential industrial strain for docosahexaenoic acid (DHA) production that contains more than 30–40 % DHA among its total fatty acids. To resolve the DHA biosynthesis mechanism and improve DHA production at a systematic level, a genomescale metabolic model (GSMM), named iCY1170_DHA, which contains 1769 reactions, 1659 metabolites, and 1170 genes, was reconstructed. Results: Based on genome annotation results and literature reports, a new DHA synthesis pathway based on a polyketide synthase (PKS) system was detected in S. limacinum. Similarly to conventional fatty acid synthesis, the biosynthesis of DHA via PKS requires abundant acetyl-CoA and NADPH. The in silico addition of malate and citrate led to increases of 24.5 % and 37.1 % in DHA production, respectively. Moreover, based on the results predicted by the model, six amino acids were shown to improve DHA production by experiment. Finally, 30 genes were identified as potential targets for DHA over-production using a Minimization of Metabolic Adjustment algorithm. The reconstructed GSMM, iCY1170_DHA, could be used to elucidate the mechanism by which DHA is synthesized in S. limacinum and predict the requirements of abundant acetyl-CoA and NADPH for DHA production as well as the enhanced yields achieved via supplementation with six amino acids, malate, and citrate.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: National High-Tech R & D Program of China; National Natural Science Foundation of China (NSFC); Program for Innovative Research Team in University; USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1626791

Journal Information:: BMC Genomics, Journal Name: BMC Genomics Journal Issue: 1 Vol. 16; ISSN 1471-2164

Publisher:: SpringerCopyright Statement

Country of Publication:: United States

Language:: English

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Schizochytrium limacinum SR21

Additional file 5: of Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/M9.FIGSHARE.C.3613970_D6 The current record is supplemented by this dataset	dataset	January 2015
Additional file 1: of Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/M9.FIGSHARE.C.3613970_D7 The current record is supplemented by this dataset	dataset	January 2015
Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/m9.figshare.c.3613970 The current record is supplemented by this collection	collection	January 2015
Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/m9.figshare.c.3613970.v1 The current record is supplemented by this collection	collection	January 2015
Additional file 7: of Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/m9.figshare.c.3613970_d1 The current record is supplemented by this dataset	dataset	January 2015
Additional file 7: of Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/m9.figshare.c.3613970_d1.v1 The current record is supplemented by this dataset	dataset	January 2015
Additional file 2: of Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/m9.figshare.c.3613970_d2 The current record is supplemented by this dataset	dataset	January 2015
Additional file 2: of Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/m9.figshare.c.3613970_d2.v1 The current record is supplemented by this dataset	dataset	January 2015
Additional file 3: of Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/m9.figshare.c.3613970_d3 The current record is supplemented by this dataset	dataset	January 2015
Additional file 3: of Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/m9.figshare.c.3613970_d3.v1 The current record is supplemented by this dataset	dataset	January 2015
Additional file 6: of Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/m9.figshare.c.3613970_d4 The current record is supplemented by this text	text	January 2015
Additional file 6: of Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/m9.figshare.c.3613970_d4.v1 The current record is supplemented by this text	text	January 2015
Additional file 8: of Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/m9.figshare.c.3613970_d5 The current record is supplemented by this dataset	dataset	January 2015
Additional file 8: of Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/m9.figshare.c.3613970_d5.v1 The current record is supplemented by this dataset	dataset	January 2015
Additional file 5: of Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/m9.figshare.c.3613970_d6.v1 The current record is supplemented by this dataset	dataset	January 2015
Additional file 1: of Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/m9.figshare.c.3613970_d7.v1 The current record is supplemented by this dataset	dataset	January 2015
Additional file 4: of Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/m9.figshare.c.3613970_d8 The current record is supplemented by this dataset	dataset	January 2015
Additional file 4: of Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production Ye, Chao; Qiao, Weihua; Yu, Xiaobin https://doi.org/10.6084/m9.figshare.c.3613970_d8.v1 The current record is supplemented by this dataset	dataset	January 2015