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

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. Petersen, Wender L. P. Bredie, Dan Staerk, Vassilios Roussis, Efstathia Ioannou () and Sotirios C. Kampranis ()
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Codruta Ignea: University of Copenhagen
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

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32921-w

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