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Expanding the terpene biosynthetic code with non-canonical 16 carbon atom building blocks

Author

Listed:
  • Codruta Ignea

    (University of Copenhagen
    McGill University, McConnell Engineering Building)

  • Morten H. Raadam

    (University of Copenhagen)

  • Aikaterini Koutsaviti

    (National and Kapodistrian University of Athens)

  • Yong Zhao

    (University of Copenhagen)

  • Yao-Tao Duan

    (University of Copenhagen)

  • Maria Harizani

    (National and Kapodistrian University of Athens)

  • Karel Miettinen

    (University of Copenhagen)

  • Panagiota Georgantea

    (National and Kapodistrian University of Athens)

  • Mads Rosenfeldt

    (University of Copenhagen)

  • Sara E. Viejo-Ledesma

    (University of Copenhagen)

  • Mikael A. Petersen

    (University of Copenhagen)

  • Wender L. P. Bredie

    (University of Copenhagen)

  • Dan Staerk

    (University of Copenhagen)

  • Vassilios Roussis

    (National and Kapodistrian University of Athens)

  • Efstathia Ioannou

    (National and Kapodistrian University of Athens)

  • Sotirios C. Kampranis

    (University of Copenhagen)

Abstract

Humankind relies on specialized metabolites for medicines, flavors, fragrances, and numerous other valuable biomaterials. However, the chemical space occupied by specialized metabolites, and, thus, their application potential, is limited because their biosynthesis is based on only a handful of building blocks. Engineering organisms to synthesize alternative building blocks will bypass this limitation and enable the sustainable production of molecules with non-canonical chemical structures, expanding the possible applications. Herein, we focus on isoprenoids and combine synthetic biology with protein engineering to construct yeast cells that synthesize 10 non-canonical isoprenoid building blocks with 16 carbon atoms. We identify suitable terpene synthases to convert these building blocks into C16 scaffolds and a cytochrome P450 to decorate the terpene scaffolds and produce different oxygenated compounds. Thus, we reconstruct the modular structure of terpene biosynthesis on 16-carbon backbones, synthesizing 28 different non-canonical terpenes, some of which have interesting odorant properties.

Suggested Citation

  • Codruta Ignea & Morten H. Raadam & Aikaterini Koutsaviti & Yong Zhao & Yao-Tao Duan & Maria Harizani & Karel Miettinen & Panagiota Georgantea & Mads Rosenfeldt & Sara E. Viejo-Ledesma & Mikael A. Pete, 2022. "Expanding the terpene biosynthetic code with non-canonical 16 carbon atom building blocks," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32921-w
    DOI: 10.1038/s41467-022-32921-w
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    References listed on IDEAS

    as
    1. Codruta Ignea & Morten H. Raadam & Mohammed S. Motawia & Antonios M. Makris & Claudia E. Vickers & Sotirios C. Kampranis, 2019. "Orthogonal monoterpenoid biosynthesis in yeast constructed on an isomeric substrate," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    2. Yasuo Yoshikuni & Thomas E. Ferrin & Jay D. Keasling, 2006. "Designed divergent evolution of enzyme function," Nature, Nature, vol. 440(7087), pages 1078-1082, April.
    Full references (including those not matched with items on IDEAS)

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