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Exploring and expanding the natural chemical space of bacterial diterpenes

Author

Listed:
  • Xiuting Wei

    (University of Florida)

  • Wenbo Ning

    (University of Florida)

  • Caitlin A. McCadden

    (University of Florida)

  • Tyler A. Alsup

    (University of Florida)

  • Zining Li

    (University of Florida
    Sichuan University)

  • Diana P. Łomowska-Keehner

    (University of Florida)

  • Jordan Nafie

    (Biotools, Inc.)

  • Tracy Qu

    (University of Florida)

  • Melvin Osei Opoku

    (University of Florida)

  • Glen R. Gillia

    (University of Florida)

  • Baofu Xu

    (University of Florida
    Chinese Academy of Sciences, Zhangjiang Hi-Tech Park
    Bohai Rim Advanced Research Institute for Drug Discovery)

  • Daniel G. Icenhour

    (University of Florida)

  • Jeffrey D. Rudolf

    (University of Florida)

Abstract

Terpenoids are the largest family of natural products but relatively rare in bacteria. Genome mining reveals widespread prevalence of terpene synthases, the enzymes responsible for constructing the hydrocarbon skeletons, in bacteria. Here, we show that 125 (37%) of 334 terpene synthases from 8 phyla, 17 classes, and 83 genera of bacteria are active as diterpene synthases. Isolation and structural elucidation of 28 diterpenes from 31 terpene synthases reveal three previously unreported terpene skeletons, skeletons of natural products from other organisms with unknown biosynthetic pathways, diterpenes that are known in other organisms but to the best of our knowledge not previously seen in bacteria, or new structural and stereochemical isomers of diterpenes. We also identify type I diterpene synthases from myxobacteria and cyanobacteria. This study will help to discover new natural products, advance studies in terpenoid biosynthesis and enzymology, and provide model systems to probe the ecological roles of terpenes.

Suggested Citation

  • Xiuting Wei & Wenbo Ning & Caitlin A. McCadden & Tyler A. Alsup & Zining Li & Diana P. Łomowska-Keehner & Jordan Nafie & Tracy Qu & Melvin Osei Opoku & Glen R. Gillia & Baofu Xu & Daniel G. Icenhour &, 2025. "Exploring and expanding the natural chemical space of bacterial diterpenes," Nature Communications, Nature, vol. 16(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57145-6
    DOI: 10.1038/s41467-025-57145-6
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    References listed on IDEAS

    as
    1. Yan Yan & Qikun Liu & Xin Zang & Shuguang Yuan & Undramaa Bat-Erdene & Calvin Nguyen & Jianhua Gan & Jiahai Zhou & Steven E. Jacobsen & Yi Tang, 2018. "Resistance-gene-directed discovery of a natural-product herbicide with a new mode of action," Nature, Nature, vol. 559(7714), pages 415-418, July.
    2. Zhong Li & Lilan Zhang & Kangwei Xu & Yuanyuan Jiang & Jieke Du & Xingwang Zhang & Ling-Hong Meng & Qile Wu & Lei Du & Xiaoju Li & Yuechan Hu & Zhenzhen Xie & Xukai Jiang & Ya-Jie Tang & Ruibo Wu & Re, 2023. "Molecular insights into the catalytic promiscuity of a bacterial diterpene synthase," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
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