Total biosynthesis of cotylenin diterpene glycosides as 14-3-3 protein–protein interaction stabilizers
Year: 2024
Type: article
Abstract: and elucidation of the biosynthetic pathway of CNs. Our investigation reveals the roles of glycosyltransferase, methyltransferase, and prenyltransferase enzymes in the assembly and modification of the saccharide moiety, as well as the multifunctional oxidation activity of the P450 enzyme CtyA. We leveraged this knowledge to achieve the total biosynthesis of not only key intermediates such as CN-C, E, F, and I, but also a novel, unnatural CN derivative using heterologous expression. This showcases the potential of pathway enzymes as catalytic tools to expand the structural diversity of diterpene glycosides. Furthermore, the stabilization effects of pathway intermediates on 14-3-3 PPIs underscore the importance of saccharide modifications in bioactivity. These findings provide a foundation for future rational synthesis of cotylenin A and other structurally diverse derivatives, broadening the scope of diterpene glycoside production.
Source: Chemical Science
DOI: 10.1039/d4sc05963h
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Funders: Innovative Research Group Project of the National Natural Science Foundation of China, National Natural Science Foundation of China, Hokkaido University, Chinesisch-Deutsche Zentrum für Wissenschaftsförderung, National Key Research and Development Program of China, Fundamental Research Funds for the Central Universities, National Science Fund for Distinguished Young Scholars, Special Project for Research and Development in Key areas of Guangdong Province, Shenzhen Science and Technology Innovation Program, Division of Chemistry
OpenAlex ID: W4404832064