TY - JOUR
T1 - Expanding the terpene biosynthetic code with non-canonical 16 carbon atom building blocks
AU - Ignea, Codruta
AU - Raadam, Morten Hessellund
AU - Koutsaviti, Aikaterini
AU - Zhao, Yong
AU - Duan, Yaotao
AU - Harizani, Maria
AU - Miettinen, Karel
AU - Georgantea, Panagiota
AU - Rosenfeldt, Mads
AU - Viejo-Ledesma, Sara E.
AU - Petersen, Mikael Agerlin
AU - Bredie, Wender
AU - Stærk, Dan
AU - Roussis, Vassilios
AU - Ioannou, Efstathia
AU - Kampranis, Sotirios
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-022-32921-w
DO - 10.1038/s41467-022-32921-w
M3 - Journal article
C2 - 36057727
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 5188
ER -