Longestin (KS‐505a), a specific inhibitor of phosphodiesterase, is a meroterpenoid that consists of a unique octacyclic terpene skeleton with branched methyl groups at unusual positions (C1 and C12). Biochemical analysis of Lon23, a methyltransferas...
Longestin (KS‐505a), a specific inhibitor of phosphodiesterase, is a meroterpenoid that consists of a unique octacyclic terpene skeleton with branched methyl groups at unusual positions (C1 and C12). Biochemical analysis of Lon23, a methyltransferase involved in the biosynthesis of longestin, demonstrated that it methylates homoisopentenyl diphosphate (homo‐IPP) to afford (3Z)‐3‐methyl IPP. This compound, along with IPP, is selectively accepted as extender units by Lon22, a geranylgeranyl diphosphate (GGPP) synthase homologue, to yield dimethylated GGPP (dmGGPP). The absolute configuration of dmGGPP was determined to be (4R,12R) by degradation and chiral GC analysis. These findings allowed us to propose an enzymatic sequence for key steps of the biosynthetic pathway of the unusual homoterpenoid longestin.
Die enzymatische Bildung von Dimethylgeranylgeranyldiphosphat (dmGGPP), einem Schlüsselintermediat der Biosynthese des ungewöhnlichen Homoterpenoids Longestin (KS‐505a), wird vorgestellt. Lon23 katalysiert die Methylierung von Isopentenyldiphosphat (IPP) zu (3Z)‐3‐Methyl‐IPP [(Z)‐homo‐IPP], das als Verlängerungseinheit bei der Lon22‐katalysierten Prenylierung genutzt wird. Diese Erkenntnisse bilden einen Ausgangspunkt für die Aufklärung der späteren Biosynthesestufen.