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A fungal NRPS-PKS enzyme catalyses the formation of the flavonoid naringenin

Author

Listed:
  • Hongjiao Zhang

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

  • Zixin Li

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

  • Shuang Zhou

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

  • Shu-Ming Li

    (Philipps-Universität Marburg)

  • Huomiao Ran

    (Chinese Academy of Sciences)

  • Zili Song

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

  • Tao Yu

    (Chinese Academy of Sciences)

  • Wen-Bing Yin

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

Abstract

Biosynthesis of the flavonoid naringenin in plants and bacteria is commonly catalysed by a type III polyketide synthase (PKS) using one p-coumaroyl-CoA and three malonyl-CoA molecules as substrates. Here, we report a fungal non-ribosomal peptide synthetase -polyketide synthase (NRPS-PKS) hybrid FnsA for the naringenin formation. Feeding experiments with isotope-labelled precursors demonstrate that FnsA accepts not only p-coumaric acid (p-CA), but also p-hydroxybenzoic acid (p-HBA) as starter units, with three or four malonyl-CoA molecules for elongation, respectively. In vitro assays and MS/MS analysis prove that both p-CA and p-HBA are firstly activated by the adenylation domain of FnsA. Phylogenetic analysis reveals that the PKS portion of FnsA shares high sequence homology with type I PKSs. Refactoring the biosynthetic pathway in yeast with the involvement of fnsA provides an alternative approach for the production of flavonoids such as isorhamnetin and acacetin.

Suggested Citation

  • Hongjiao Zhang & Zixin Li & Shuang Zhou & Shu-Ming Li & Huomiao Ran & Zili Song & Tao Yu & Wen-Bing Yin, 2022. "A fungal NRPS-PKS enzyme catalyses the formation of the flavonoid naringenin," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34150-7
    DOI: 10.1038/s41467-022-34150-7
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    References listed on IDEAS

    as
    1. Quanli Liu & Tao Yu & Xiaowei Li & Yu Chen & Kate Campbell & Jens Nielsen & Yun Chen, 2019. "Rewiring carbon metabolism in yeast for high level production of aromatic chemicals," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    2. Choong-Soo Yun & Takayuki Motoyama & Hiroyuki Osada, 2015. "Biosynthesis of the mycotoxin tenuazonic acid by a fungal NRPS–PKS hybrid enzyme," Nature Communications, Nature, vol. 6(1), pages 1-9, December.
    3. Xiaonan Liu & Jian Cheng & Guanghui Zhang & Wentao Ding & Lijin Duan & Jing Yang & Ling Kui & Xiaozhi Cheng & Jiangxing Ruan & Wei Fan & Junwen Chen & Guangqiang Long & Yan Zhao & Jing Cai & Wen Wang , 2018. "Engineering yeast for the production of breviscapine by genomic analysis and synthetic biology approaches," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
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