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De novo biosynthesis of the hops bioactive flavonoid xanthohumol in yeast

Author

Listed:
  • Shan Yang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Ruibing Chen

    (Chinese Academy of Sciences)

  • Xuan Cao

    (Chinese Academy of Sciences)

  • Guodong Wang

    (Chinese Academy of Sciences)

  • Yongjin J. Zhou

    (Chinese Academy of Sciences
    Chinese Academy of Sciences
    Chinese Academy of Sciences)

Abstract

The flavonoid xanthohumol is an important flavor substance in the brewing industry that has a wide variety of bioactivities. However, its unstable structure results in its low content in beer. Microbial biosynthesis is considered a sustainable and economically viable alternative. Here, we harness the yeast Saccharomyces cerevisiae for the de novo biosynthesis of xanthohumol from glucose by balancing the three parallel biosynthetic pathways, prenyltransferase engineering, enhancing precursor supply, constructing enzyme fusion, and peroxisomal engineering. These strategies improve the production of the key xanthohumol precursor demethylxanthohumol (DMX) by 83-fold and achieve the de novo biosynthesis of xanthohumol in yeast. We also reveal that prenylation is the key limiting step in DMX biosynthesis and develop tailored metabolic regulation strategies to enhance the DMAPP availability and prenylation efficiency. Our work provides feasible approaches for systematically engineering yeast cell factories for the de novo biosynthesis of complex natural products.

Suggested Citation

  • Shan Yang & Ruibing Chen & Xuan Cao & Guodong Wang & Yongjin J. Zhou, 2024. "De novo biosynthesis of the hops bioactive flavonoid xanthohumol in yeast," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44654-5
    DOI: 10.1038/s41467-023-44654-5
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