Transcriptome analysis reveals that up-regulation of the fatty acid synthase gene promotes the accumulation of docosahexaenoic acid in Schizochytrium sp. S056 when glycerol is used

Abstract A comparison of the glycerol and glucose effect on the fermentation of Schizochytrium sp. S056 indicated that glycerol increased the docosahexaenoic acid (DHA) concentration of the total fatty acids to 52.28% which was 31.75% higher than that produced by glucose. The underlying mechanism of the DHA content increase by the glycerol treatment, however, remains to be clarified. Transcriptome analysis was used to study the effect of the carbon source on genetic regulation and metabolism. These results revealed that when Schizochytrium sp. S056 was cultured with glycerol, the glycolysis and branched-chain amino acids (valine, leucine, and isoleucine) metabolism-associated genes were substantially up-regulated, resulting in increased overall acetyl-CoA production. Additionally, genes involved in the gluconeogenesis, pentose phosphate and citric acid cycle pathways were significantly down-regulated, resulting in more acetyl-CoA for fatty acid formation. Specifically, the expression of the fatty acid synthase (FAS) gene, which is involved in fatty acid biosynthesis, was up-regulated by the glycerol-increased production of acetyl-CoA. Accordingly, the enhanced FAS system led to a significant increase of the content of DHA. Therefore, overexpression of the FAS gene favors the accumulation of DHA. Furthermore, these results were also corroborated through the inhibition of the FAS system by cerulenin treatment.