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Synthetic biology based construction of biological activity-related library of fungal decalin-containing diterpenoid pyrones

Author

Listed:
  • Kento Tsukada

    (The University of Tokyo, Komaba, Meguro-ku)

  • Shono Shinki

    (The University of Tokyo, Komaba, Meguro-ku)

  • Akiho Kaneko

    (The University of Tokyo, Komaba, Meguro-ku)

  • Kazuma Murakami

    (Kyoto University)

  • Kazuhiro Irie

    (Kyoto University)

  • Masatoshi Murai

    (Kyoto University)

  • Hideto Miyoshi

    (Kyoto University)

  • Shingo Dan

    (Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku)

  • Kumi Kawaji

    (Tohoku University, 2-1, Seiryocho, Aoba-ku)

  • Hironori Hayashi

    (Tohoku University, 2-1, Seiryocho, Aoba-ku)

  • Eiichi N. Kodama

    (Tohoku University, 2-1, Seiryocho, Aoba-ku
    Tohoku University, 2-1, Seiryocho, Aoba-ku)

  • Aki Hori

    (Kanazawa University)

  • Emil Salim

    (Kanazawa University)

  • Takayuki Kuraishi

    (Kanazawa University)

  • Naoya Hirata

    (Tonomachi, Kawasaki-ku)

  • Yasunari Kanda

    (Tonomachi, Kawasaki-ku)

  • Teigo Asai

    (The University of Tokyo, Komaba, Meguro-ku
    Tohoku University, Aoba-yama, Aoba-ku)

Abstract

A synthetic biology method based on heterologous biosynthesis coupled with genome mining is a promising approach for increasing the opportunities to rationally access natural product with novel structures and biological activities through total biosynthesis and combinatorial biosynthesis. Here, we demonstrate the advantage of the synthetic biology method to explore biological activity-related chemical space through the comprehensive heterologous biosynthesis of fungal decalin-containing diterpenoid pyrones (DDPs). Genome mining reveals putative DDP biosynthetic gene clusters distributed in five fungal genera. In addition, we design extended DDP pathways by combinatorial biosynthesis. In total, ten DDP pathways, including five native pathways, four extended pathways and one shunt pathway, are heterologously reconstituted in a genetically tractable heterologous host, Aspergillus oryzae, resulting in the production of 22 DDPs, including 15 new analogues. We also demonstrate the advantage of expanding the diversity of DDPs to probe various bioactive molecules through a wide range of biological evaluations.

Suggested Citation

  • Kento Tsukada & Shono Shinki & Akiho Kaneko & Kazuma Murakami & Kazuhiro Irie & Masatoshi Murai & Hideto Miyoshi & Shingo Dan & Kumi Kawaji & Hironori Hayashi & Eiichi N. Kodama & Aki Hori & Emil Sali, 2020. "Synthetic biology based construction of biological activity-related library of fungal decalin-containing diterpenoid pyrones," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15664-4
    DOI: 10.1038/s41467-020-15664-4
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    Cited by:

    1. Jia Tang & Yudai Matsuda, 2024. "Discovery of fungal onoceroid triterpenoids through domainless enzyme-targeted global genome mining," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Charlotte Cautereels & Jolien Smets & Peter Bircham & Dries De Ruysscher & Anna Zimmermann & Peter De Rijk & Jan Steensels & Anton Gorkovskiy & Joleen Masschelein & Kevin J. Verstrepen, 2024. "Combinatorial optimization of gene expression through recombinase-mediated promoter and terminator shuffling in yeast," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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