Recently, our group established a sesquiterpenoid platform by extensively rewiring the nonconventional yeast Ogataea polymorpha for β-elemene production.

β-Elemene, a sesquiterpenoid from the traditional Chinese herb Rhizoma zedoariae, has been widely applied in cancer therapies with a market value of over 4 billion CNY. Currently, the production of β-elemene is depending on the traditional plant extraction that cannot meet the market demand. Alternatively, microbial cell factories may provide a feasible route for sustainable production of β-elemene toward industrial application.

O. polymorpha, a nonconventional Crabtree-negative microorganism, possesses numerous advantages, such as high-density fermentation, and thermal tolerance (the maximum tolerated temperature is 50℃), which are beneficial for constructing superior cell factories. In this study, global metabolic rewiring of O. polymorpha was achieved by optimizing the MVA pathway and enhancing the supply of acetyl-CoA and NADPH. Finally, the highest titers of 4.7 g/L were obtained in fed-batch fermentations in shake-flask. This work proved the potential of O. polymorpha as a chassis cell for production of sesquiterpenoids and other acetyl-CoA derived chemicals, which might contribute to the large-scale production of β-elemene in industries.

This study was published in Metabolic Engineering on Feb. 22. This work was supported by the National Key Research and Development Project and the Innovation Grant of Dalian Institute of Chemical Physics CAS. (Text and image by Min Ye)

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