Fermentation performance and metabolomic analysis of an engineered high-yield PUFA-producing strain of Schizochytrium sp.

Abstract

The ω-3/long-chain polyunsaturated fatty acids (LC-PUFAs) play an important role in human health, but they cannot be synthesized in sufficient amounts by the human body. In a previous study, we obtained an engineered Schizochytrium sp. strain (HX-RS) by exchanging the acyltransferase (AT) gene, and it was able to co-produce docosahexaenoic acid and eicosapentaenoic acid. To investigate the mechanism underlying the increase of PUFA content in HX-RS, the discrepancies of fermentation performance, key enzyme activities and intracellular metabolites between HX-RS and its wild-type parent strain (WTS) were analyzed via fed-batch fermentation in 5-L bioreactors. The results showed that the cell dry weight (CDW) of HX-RS was higher than that of the WTS. Metabolomics combined with multivariate analysis showed that 4-aminobutyric acid, proline and glutamine are potential biomarkers associated with cell growth and lipid accumulation of HX-RS. Additionally, the shift of metabolic flux including a decrease of glyceraldehyde-3-phosphate content, high flux from pyruvate to acetyl-CoA, and a highly active glycolysis pathway were also found to be closely related to the high PUFA yield of the engineered strain. These findings provide new insights into the effects of exogenous AT gene expression on cell proliferation and fatty acid metabolism.