Total Biosynthesis of Cotylenin Diterpene Glycosides as 14-3-3 Protein-Protein Interaction Stabilizers

Cotylenins (CNs) are bioactive fungal diterpene glycosides that exhibit stabilizing activity on 14-3-3 protein-protein interactions (PPIs), which has significant therapeutic potential. Although CNs were isolated as early as 1970, their biosynthetic pathway has remained unclear, and their limited supply has hindered further research. Here, we report the identification of the biosynthetic gene cluster