Combinatorial biosynthesis in yeast leads to over 200 diterpenoids.
Metab Eng
; 82: 193-200, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38387676
ABSTRACT
Diterpenoids form a diverse group of natural products, many of which are or could become pharmaceuticals or industrial chemicals. The modular character of diterpene biosynthesis and the promiscuity of the enzymes involved make combinatorial biosynthesis a promising approach to generate libraries of diverse diterpenoids. Here, we report on the combinatorial assembly in yeast of ten diterpene synthases producing (+)-copalyl diphosphate-derived backbones and four cytochrome P450 oxygenases (CYPs) in diverse combinations. This resulted in the production of over 200 diterpenoids. Based on literature and chemical database searches, 162 of these compounds can be considered new-to-Nature. The CYPs accepted most substrates they were given but remained regioselective with few exceptions. Our results provide the basis for the systematic exploration of the diterpenoid chemical space in yeast using sequence databases.
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Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
/
Diterpenos
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article