taxadiene

Taxadiene (taxa-4(5),11(12)-diene) is a bicyclic diterpene hydrocarbon that serves as the first dedicated intermediate in the biosynthesis of paclitaxel (taxol). The molecule contains 20 carbon atoms arranged in a fused bicyclic skeleton and bears two nonconjugated double bonds, as indicated by its name.

Natural occurrence and biosynthesis: Taxadiene is produced in Taxus species (yews) from geranylgeranyl pyrophosphate (GGPP) through cyclization catalyzed by the enzyme taxadiene synthase. This enzymatic step commits the taxane biosynthetic pathway to paclitaxel production. Following formation of taxadiene, a series of oxidation, cyclization, and side-chain attachment reactions transforms it into taxane intermediates that eventually yield paclitaxel.

Applications and significance: Taxadiene is the first dedicated precursor in paclitaxel biosynthesis and remains a focal point in efforts to produce paclitaxel via biotechnology. Because natural extraction of paclitaxel from yews is inefficient, taxadiene is now produced in engineered microorganisms and plant cell cultures to supply precursors for semi-synthetic paclitaxel production. The compound also serves as a model substrate for studying terpene cyclases and taxane pathway enzymes, and it can be used to gauge pathway flux in metabolic engineering projects.