This technology involves a recombinant Saccharomyces cerevisiae strain in which the endogenous UPC2 gene is replaced with a mutant variant having low ergosterol binding affinity using the CRISPR-Cas9 system. The mutant transcriptional regulator activates the entire sterol biosynthetic pathway, thereby increasing the production of sterol precursors.
While yeast is a proven safe industrial host, the accumulation of ergosterol triggers feedback inhibition via Upc2p, which limits the sterol biosynthetic pathway. This has historically hindered the mass production of sterol precursors, which serve as raw materials for ginsenosides and bile acid-based pharmaceuticals, in yeast.
By replacing the gene directly on the chromosome rather than using a plasmid, this technology maintains optimal expression levels and alleviates feedback regulation, significantly increasing the production of precursors such as epoxysqualene and squalene. The strain is stable, making it an ideal host for further metabolic engineering. It can be applied to the production of dammarenediol, a precursor for the immune-boosting ginsenosides, and UDCA, a treatment for liver disease, ensuring both supply stability and cost competitiveness compared to plant extraction or chemical synthesis.
This invention was developed with support from the Ministry of Science and ICT for research on constructing artificial regulatory circuits for the development of high-efficiency yeast cell factories.
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