Integrating pathway elucidation with yeast engineering to produce polpunonic acid the precursor of the anti-obesity agent celastrol

摘要

Proposed celastrol biosynthetic pathway. Dashed arrows depict multiple enzymatic steps. Friedelin synthase (FRS) performs the first committed step of the pathway by cyclization of the common triterpenoid precursor 2,3-oxidosqualene into friedelin. Next, CYP712K1, CYP712K2 or CYP712K3 catalyzes successive oxygenations of friedelin to form polpunonic acid ( ) via 29-hydroxy-friedelin ( ) and 29-oxo-friedelin ( ). Enzymes of different types are proposed to perform the rest of the reactions to obtain celastrol