Harnessing transcription factor Mga2 and fatty acid elongases to overproduce palmitoleic acid in Saccharomyces cerevisiae

As a long chain monounsaturated fatty acid, palmitoleic acid (POA) can be widely applied in medicine, food and industry. However, the limited natural sources and relatively low content thereof constrain the widespread use of POA. Here we presented the construction of a Saccharomyces cerevisiae platform strain for high-level production of POA. Transcription factor Mga2 increased the contents of POA and total unsaturated fatty acids by significantly upregulating the expression of genes encoding key enzymes in fatty acid anabolism, and the truncated Mga2 exhibited stronger capability to improve POA and oleic acid content than the whole Mga2. The fatty acid elongases investigated displayed distinct effects on the synthesis of POA. Through optimizing the combinatorial expression of fatty acid elongases and Mga2, we successfully established a high POA content of 58.5% (v/v) in the recombinants. The highest POA titer of 928 mg/L was obtained at 144 h in flask culture. These findings enhance our understanding of Mga2 regulation and provide a novel approach to engineer S. cerevisiae for sustainable production of POA or its derivatives.