title: Reconstruction and analysis of the genome-scale metabolic model of schizochytrium limacinum SR21 for docosahexaenoic acid production.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
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. qiaoweihua2012@163.com.|The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. qiaoweihua2012@163.com.
authors.forename: Weihua
authors.initials: W
authors.lastname: Qiao
authors.affiliation: The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China. xbyu@jiangnan.edu.cn.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing, 211816, China. xiaojunji@njtech.edu.cn.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing, 211816, China. huangh@njtech.edu.cn.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: School of Marine and Atmospheric Sciences, Stony Brook University, Stony Brook, NY, USA. jackie.collier@stonybrook.edu.
authors.forename: Jackie L
authors.initials: JL
authors.lastname: Collier
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: D019149:Bioreactors; D053898:Biosynthetic Pathways / Q000235:genetics; D004281:Docosahexaenoic Acids / Q000096:biosynthesis* / Q000235:genetics; D005227:Fatty Acids / Q000096:biosynthesis* / Q000235:genetics; D005285:Fermentation; D060847:Metabolic Engineering; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism*; D058009:Stramenopiles / Q000235:genetics / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D004281:Docosahexaenoic Acids; D048630:Polyketide Synthases