Abstract
The novel diterpenoid taxol (paclitaxel) is now well-established as a potent chemotherapeutic
agent. Total synthesis of the drug is not commercially feasible and, in the foreseeable
future, the supply of taxol and its synthetically useful progenitors must rely on
biological methods of production. The first three steps of taxol biosynthesis have
been defined and the responsible enzymes described. These are the cyclization of the
universal diterpenoid precursor geranylgeranyl diphosphate to taxa-4(5),11(12)-diene,
the cytochrome P450-catalyzed hydroxylation of this olefin to taxa-4(20),11(12)-dien-5α-ol,
and the acetyl CoA-dependent conversion of the alcohol to the corresponding acetate
ester. Demonstration of these early steps of taxol biosynthesis suggests that the
complete pathway can be defined by a systematic, stepwise approach at the cell-free
enzyme level. When combined with in vivo studies to determine contribution to pathway flux, slow steps can be targeted for
gene isolation and subsequent overexpression in Taxus to improve the yield of taxol and related compounds.
Key words
Taxol - paclitaxel - biosynthesis - taxadiene synthase - taxadiene hydroxylase - taxadienol
acetyltransferase
