IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-47968-0.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-47968-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-47968-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Prashanth Srinivasan & Christina D. Smolke, 2020. "Biosynthesis of medicinal tropane alkaloids in yeast," Nature, Nature, vol. 585(7826), pages 614-619, September.
    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. Radin Sadre & Thilani M. Anthony & Josh M. Grabar & Matthew A. Bedewitz & A. Daniel Jones & Cornelius S. Barry, 2022. "Metabolomics-guided discovery of cytochrome P450s involved in pseudotropine-dependent biosynthesis of modified tropane alkaloids," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    4. Prashant D. Sonawane & Sachin A. Gharat & Adam Jozwiak & Ranjit Barbole & Sarah Heinicke & Efrat Almekias-Siegl & Sagit Meir & Ilana Rogachev & Sarah E. O’ Connor & Ashok P. Giri & Asaph Aharoni, 2023. "A BAHD-type acyltransferase concludes the biosynthetic pathway of non-bitter glycoalkaloids in ripe tomato fruit," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Matthew A. Bedewitz & A. Daniel Jones & John C. D’Auria & Cornelius S. Barry, 2018. "Tropinone synthesis via an atypical polyketide synthase and P450-mediated cyclization," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    6. Colin Y. Kim & Andrew J. Mitchell & David W. Kastner & Claire E. Albright & Michael A. Gutierrez & Christopher M. Glinkerman & Heather J. Kulik & Jing-Ke Weng, 2023. "Emergence of a proton exchange-based isomerization and lactonization mechanism in the plant coumarin synthase COSY," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    8. Rao Fu & Pingyu Zhang & Ge Jin & Lianglei Wang & Shiqian Qi & Yang Cao & Cathie Martin & Yang Zhang, 2021. "Versatility in acyltransferase activity completes chicoric acid biosynthesis in purple coneflower," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. 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.
    2. Radin Sadre & Thilani M. Anthony & Josh M. Grabar & Matthew A. Bedewitz & A. Daniel Jones & Cornelius S. Barry, 2022. "Metabolomics-guided discovery of cytochrome P450s involved in pseudotropine-dependent biosynthesis of modified tropane alkaloids," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Wenna Li & Zhao Zhou & Xianglai Li & Lin Ma & Qingyuan Guan & Guojun Zheng & Hao Liang & Yajun Yan & Xiaolin Shen & Jia Wang & Xinxiao Sun & Qipeng Yuan, 2022. "Biosynthesis of plant hemostatic dencichine in Escherichia coli," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    4. 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.
    5. 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.
    6. Yue Gao & Fei Li & Zhengshan Luo & Zhiwei Deng & Yan Zhang & Zhenbo Yuan & Changmei Liu & Yijian Rao, 2024. "Modular assembly of an artificially concise biocatalytic cascade for the manufacture of phenethylisoquinoline alkaloids," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. Simon d’Oelsnitz & Daniel J. Diaz & Wantae Kim & Daniel J. Acosta & Tyler L. Dangerfield & Mason W. Schechter & Matthew B. Minus & James R. Howard & Hannah Do & James M. Loy & Hal S. Alper & Y. Jessie, 2024. "Biosensor and machine learning-aided engineering of an amaryllidaceae enzyme," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    8. Ye Yuan & Lei Chen & Kexu Song & Miaomiao Cheng & Ling Fang & Lingfei Kong & Lanlan Yu & Ruonan Wang & Zhendong Fu & Minmin Sun & Qian Wang & Chengjun Cui & Haojue Wang & Jiuyang He & Xiaonan Wang & Y, 2024. "Stable peptide-assembled nanozyme mimicking dual antifungal actions," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    9. Ivica Odorčić & Mohamed Belal Hamed & Sam Lismont & Lucía Chávez-Gutiérrez & Rouslan G. Efremov, 2024. "Apo and Aβ46-bound γ-secretase structures provide insights into amyloid-β processing by the APH-1B isoform," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    10. Léon Faure & Bastien Mollet & Wolfram Liebermeister & Jean-Loup Faulon, 2023. "A neural-mechanistic hybrid approach improving the predictive power of genome-scale metabolic models," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    11. Xiang Jiao & Xiaozhi Fu & Qishuang Li & Junling Bu & Xiuyu Liu & Otto Savolainen & Luqi Huang & Juan Guo & Jens Nielsen & Yun Chen, 2024. "De novo production of protoberberine and benzophenanthridine alkaloids through metabolic engineering of yeast," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    12. Tian Zhu & Merry H. Ma, 2022. "Deriving the Optimal Strategy for the Two Dice Pig Game via Reinforcement Learning," Stats, MDPI, vol. 5(3), pages 1-14, August.
    13. Stella Vitt & Simone Prinz & Martin Eisinger & Ulrich Ermler & Wolfgang Buckel, 2022. "Purification and structural characterization of the Na+-translocating ferredoxin: NAD+ reductase (Rnf) complex of Clostridium tetanomorphum," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    14. Pierre Azoulay & Joshua Krieger & Abhishek Nagaraj, 2024. "Old Moats for New Models: Openness, Control, and Competition in Generative AI," NBER Chapters, in: Entrepreneurship and Innovation Policy and the Economy, volume 4, National Bureau of Economic Research, Inc.
    15. Riya Shah & Thomas C. Panagiotou & Gregory B. Cole & Trevor F. Moraes & Brigitte D. Lavoie & Christopher A. McCulloch & Andrew Wilde, 2024. "The DIAPH3 linker specifies a β-actin network that maintains RhoA and Myosin-II at the cytokinetic furrow," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    16. Yashan Yang & Qianqian Shao & Mingcheng Guo & Lin Han & Xinyue Zhao & Aohan Wang & Xiangyun Li & Bo Wang & Ji-An Pan & Zhenguo Chen & Andrei Fokine & Lei Sun & Qianglin Fang, 2024. "Capsid structure of bacteriophage ΦKZ provides insights into assembly and stabilization of jumbo phages," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    17. Anthony C. Bishop & Glorisé Torres-Montalvo & Sravya Kotaru & Kyle Mimun & A. Joshua Wand, 2023. "Robust automated backbone triple resonance NMR assignments of proteins using Bayesian-based simulated annealing," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    18. Bret M. Boyd & Ian James & Kevin P. Johnson & Robert B. Weiss & Sarah E. Bush & Dale H. Clayton & Colin Dale, 2024. "Stochasticity, determinism, and contingency shape genome evolution of endosymbiotic bacteria," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    19. Jun-Yu Si & Yuan-Mei Chen & Ye-Hui Sun & Meng-Xue Gu & Mei-Ling Huang & Lu-Lu Shi & Xiao Yu & Xiao Yang & Qing Xiong & Cheng-Bao Ma & Peng Liu & Zheng-Li Shi & Huan Yan, 2024. "Sarbecovirus RBD indels and specific residues dictating multi-species ACE2 adaptiveness," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    20. Deyun Qiu & Jinxin V. Pei & James E. O. Rosling & Vandana Thathy & Dongdi Li & Yi Xue & John D. Tanner & Jocelyn Sietsma Penington & Yi Tong Vincent Aw & Jessica Yi Han Aw & Guoyue Xu & Abhai K. Tripa, 2022. "A G358S mutation in the Plasmodium falciparum Na+ pump PfATP4 confers clinically-relevant resistance to cipargamin," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47968-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.