Overproducing nervonic acid by synergism of fatty acid elongases in engineered Saccharomyces cerevisiae

As the best dietary supplement, nervonic acid (NA) can be applied for the prevention and treatment of neurodegenerative diseases. However, the limited natural sources and high processing costs restrict the wide use of NA. Herein, we engineered Saccharomyces cerevisiae for the effective production of NA. Individual expression of fatty acid elongase from multiple species led to the synthesis of NA. NA biosynthesis was further augmented by co-expression of fatty acid elongases and knockout of elo2 . Under the optimized conditions, the recombinant produced up to 57 mg/L of NA in flask culture. Quantitative real-time PCR results indicated that the expression levels of genes encoding key enzymes in NA synthesis were significantly increased under the optimized conditions. This work may serve as a baseline to employ S. cerevisiae chassis for sustainable production of NA or its derivatives. • The effects of various fatty acid elongases on the chain length of fatty acids were compared. • The synergism of fatty acid elongases could boost the synthesis of nervonic acid. • A high nervonic acid titer of 57 mg/L was obtained in the engineered yeast.