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Discovering a mitochondrion-localized BAHD acyltransferase involved in calystegine biosynthesis and engineering the production of 3β-tigloyloxytropane

Author

Listed:
  • Junlan Zeng

    (Southwest University)

  • Xiaoqiang Liu

    (Southwest University)

  • Zhaoyue Dong

    (Southwest University)

  • Fangyuan Zhang

    (Southwest University)

  • Fei Qiu

    (Southwest University)

  • Mingyu Zhong

    (Southwest University)

  • Tengfei Zhao

    (Southwest University)

  • Chunxian Yang

    (Southwest University)

  • Lingjiang Zeng

    (Southwest University)

  • Xiaozhong Lan

    (Xizang Agricultural and Animal Husbandry College)

  • Hongbo Zhang

    (Tobacco Research Institute of Chinese Academy of Agricultural Sciences)

  • Junhui Zhou

    (China Academy of Chinese Medical Sciences)

  • Min Chen

    (Southwest University)

  • Kexuan Tang

    (Southwest University
    Shanghai Jiao Tong University)

  • Zhihua Liao

    (Southwest University)

Abstract

Solanaceous plants produce tropane alkaloids (TAs) via esterification of 3α- and 3β-tropanol. Although littorine synthase is revealed to be responsible for 3α-tropanol esterification that leads to hyoscyamine biosynthesis, the genes associated with 3β-tropanol esterification are unknown. Here, we report that a BAHD acyltransferase from Atropa belladonna, 3β-tigloyloxytropane synthase (TS), catalyzes 3β-tropanol and tigloyl-CoA to form 3β-tigloyloxytropane, the key intermediate in calystegine biosynthesis and a potential drug for treating neurodegenerative disease. Unlike other cytosolic-localized BAHD acyltransferases, TS is localized to mitochondria. The catalytic mechanism of TS is revealed through molecular docking and site-directed mutagenesis. Subsequently, 3β-tigloyloxytropane is synthesized in tobacco. A bacterial CoA ligase (PcICS) is found to synthesize tigloyl-CoA, an acyl donor for 3β-tigloyloxytropane biosynthesis. By expressing TS mutant and PcICS, engineered Escherichia coli synthesizes 3β-tigloyloxytropane from tiglic acid and 3β-tropanol. This study helps to characterize the enzymology and chemodiversity of TAs and provides an approach for producing 3β-tigloyloxytropane.

Suggested Citation

  • Junlan Zeng & Xiaoqiang Liu & Zhaoyue Dong & Fangyuan Zhang & Fei Qiu & Mingyu Zhong & Tengfei Zhao & Chunxian Yang & Lingjiang Zeng & Xiaozhong Lan & Hongbo Zhang & Junhui Zhou & Min Chen & Kexuan Ta, 2024. "Discovering a mitochondrion-localized BAHD acyltransferase involved in calystegine biosynthesis and engineering the production of 3β-tigloyloxytropane," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47968-0
    DOI: 10.1038/s41467-024-47968-0
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    References listed on IDEAS

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