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

Codruta Ignea, Morten Hessellund Raadam, Aikaterini Koutsaviti, Yong Zhao, Yaotao Duan, Maria Harizani, Karel Miettinen, Panagiota Georgantea, Mads Rosenfeldt, Sara E. Viejo-Ledesma, Mikael Agerlin Petersen, Wender Bredie, Dan Stærk, Vassilios Roussis, Efstathia Ioannou, Sotirios Kampranis*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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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.
Original languageEnglish
Article number5188
JournalNature Communications
Volume13
Number of pages16
ISSN2041-1723
DOIs
Publication statusPublished - 2022

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