Regulation of Ethanol Assimilation for Efficient Accumulation of Squalene in Saccharomyces cerevisiae .

Squalene is a triterpene that can be obtained from fish and plant oils. It is important in cosmetics and vaccines and is a precursor for many high-value terpenes and steroids. In order to increase squalene accumulation, the mevalonate pathway was systematically enhanced. Accumulation of squalene tended to increase when ethanol was added as a carbon source during fermentation, but a high concentration of ethanol affected both the strain growth and accumulation of products. By overexpressing the key trehalose synthesis gene TPS 1 and the heat shock protein gene HSP 104, the content of trehalose by Saccharomyces cerevisiae ( S. cerevisiae ) was enhanced, and stress caused by ethanol was relieved. The OD 600 value of the modified S. cerevisiae strain was increased by 80.2%, its ethanol tolerance was increased to 30 g/L, and it retained excellent activity with 50 g/L ethanol. After optimizing the fermentation conditions, the squalene titer in a 5 L bioreactor reached 27.3 g/L and the squalene content was 650 mg/g dry cell weight, the highest squalene production parameters reported to date for a microorganism.