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Tropane alkaloids biosynthesis involves an unusual type III polyketide synthase and non-enzymatic condensation

Author

Listed:
  • Jian-Ping Huang

    (Chinese Academy of Sciences)

  • Chengli Fang

    (Chinese Academy of Sciences)

  • Xiaoyan Ma

    (Chinese Academy of Sciences
    Sichuan University of Science & Engineering)

  • Li Wang

    (Chinese Academy of Sciences)

  • Jing Yang

    (Chinese Academy of Sciences)

  • Jianying Luo

    (Chinese Academy of Sciences)

  • Yijun Yan

    (Chinese Academy of Sciences)

  • Yu Zhang

    (Chinese Academy of Sciences)

  • Sheng-Xiong Huang

    (Chinese Academy of Sciences)

Abstract

The skeleton of tropane alkaloids is derived from ornithine-derived N-methylpyrrolinium and two malonyl-CoA units. The enzymatic mechanism that connects N-methylpyrrolinium and malonyl-CoA units remains unknown. Here, we report the characterization of three pyrrolidine ketide synthases (PYKS), AaPYKS, DsPYKS, and AbPYKS, from three different hyoscyamine- and scopolamine-producing plants. By examining the crystal structure and biochemical activity of AaPYKS, we show that the reaction mechanism involves PYKS-mediated malonyl-CoA condensation to generate a 3-oxo-glutaric acid intermediate that can undergo non-enzymatic Mannich-like condensation with N-methylpyrrolinium to yield the racemic 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid. This study therefore provides a long sought-after biosynthetic mechanism to explain condensation between N-methylpyrrolinium and acetate units and, more importantly, identifies an unusual plant type III polyketide synthase that can only catalyze one round of malonyl-CoA condensation.

Suggested Citation

  • Jian-Ping Huang & Chengli Fang & Xiaoyan Ma & Li Wang & Jing Yang & Jianying Luo & Yijun Yan & Yu Zhang & Sheng-Xiong Huang, 2019. "Tropane alkaloids biosynthesis involves an unusual type III polyketide synthase and non-enzymatic condensation," Nature Communications, Nature, vol. 10(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11987-z
    DOI: 10.1038/s41467-019-11987-z
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    Cited by:

    1. Fangyuan Zhang & Fei Qiu & Junlan Zeng & Zhichao Xu & Yueli Tang & Tengfei Zhao & Yuqin Gou & Fei Su & Shiyi Wang & Xiuli Sun & Zheyong Xue & Weixing Wang & Chunxian Yang & Lingjiang Zeng & Xiaozhong , 2023. "Revealing evolution of tropane alkaloid biosynthesis by analyzing two genomes in the Solanaceae family," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Tian Tian & Yong-Jiang Wang & Jian-Ping Huang & Jie Li & Bingyan Xu & Yin Chen & Li Wang & Jing Yang & Yijun Yan & Sheng-Xiong Huang, 2022. "Catalytic innovation underlies independent recruitment of polyketide synthases in cocaine and hyoscyamine biosynthesis," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    3. Jiao Yang & Ying Wu & Pan Zhang & Jianxiang Ma & Ying Jun Yao & Yan Lin Ma & Lei Zhang & Yongzhi Yang & Changmin Zhao & Jihua Wu & Xiangwen Fang & Jianquan Liu, 2023. "Multiple independent losses of the biosynthetic pathway for two tropane alkaloids in the Solanaceae family," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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