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

• Published in: BMC genomics Vol. 16; no. 1; p. 799
• Main Authors: Ye, Chao, Qiao, Weihua, Yu, Xiaobin, Ji, Xiaojun, Huang, He, Collier, Jackie L, Liu, Liming
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 16.10.2015; BioMed Central; Springer
• Subjects: BASIC BIOLOGICAL SCIENCES; Bioreactors; Biosynthetic Pathways - genetics; Biotechnology & Applied Microbiology; Docosahexaenoic acid; Docosahexaenoic Acids - biosynthesis; Docosahexaenoic Acids - genetics; Fatty Acids - biosynthesis; Fatty Acids - genetics; Fermentation; Genetics & Heredity; Genome-scale metabolic model; Genomics; Metabolic Engineering; Minimization of metabolic adjustment algorithm; Polyketide synthase system; Polyketide Synthases - genetics; Polyketide Synthases - metabolism; Schizochytrium limacinum SR21; Stramenopiles - genetics; Stramenopiles - metabolism
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-015-2042-y

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. 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.