Enzymatic synthesis of diterpene, aphidicolin (ACL), a specific inhibitor of DNA polymerase α has been studied. cDNA encoding aphidicolin-16β-ol synthase (ACS) has been cloned and overexpressed in Escherichia coli. Partially purified enzyme converted geranylgeranyl diphosphate to tetracyclic diterpene, aphidicolan-16β-ol. This enzyme also converted syn-copalyl diphosphate (syn-CDP) to aphidicolan-16β-ol, supporting intermediacy of syn-CDP. The mycelial extract of an ACL producer, Phoma betae afforded a number of diterpene hydrocarbons. Their structures suggested that these are originated from the corresponding cation intermediates. Based on this observation, a cyclization mechanism of the reaction catalyzed by ACS was proposed.
