The process starts with the large molecule 10-Deacetylbaccatin III (or 10-DAB), a natural compound found in abundance in the needles of the English yew, a common European shrub. 10-DAB is the “heart” of the Taxol molecule, which has a distinctive appendage known as an ester side-chain. Until Holton's breakthrough, attaching this side-chain of just 34 atoms to the 10-DAB mother molecule in the lab had never been practical.
Holton's team first found a way to bind the ester side-chain so that it would be small enough to enter a particular cavity within the convoluted body of the 10-DAB molecule where it could attach to a key site, known as the C-13 hydroxyl group, shown here as “OH.”
The team subsequently discovered a way to greatly speed up the process and make it far more efficient by treating the combination process with a metal alkoxide catalyst. This MAP (metal alkoxide process) catapulted Taxol into the world's best-selling anti-cancer drug by 1994, generating world-wide sales approaching $10 billion by 2000.