It has been shown that the diverse

It has been shown that the diverse structures of the cyclic diterpenes arise by di}erent modes of
cyclization of GGPP then by oxidation of the cyclization products[ Details of these processes are
emerging through the puri_cation and cloning of the enzymes involved[
Four types of GGPP cyclases have been cloned and the function of their gene products has been
determined[ Thus four types of cyclization of GGPP have been established depending on the
initiation of cyclization "protonation or diphosphate ionization#[ Furthermore each of the four
classes of cyclases are multifunctional catalyzing a series of steps on the enzyme surface[ Since these
enzymes can now be overexpressed in vitro detailed study of the mechanisms of cyclization can be
anticipated[ Rapid advances in the characterization of other cyclases can also be anticipated using
conserved sequences of the known genes and PCR[ Questions of particular interest to be addressed
are the existence of enantiomeric products of the cyclization of GGPP and the diastereotopic
cyclization of the 55!bicyclic products from the proton!initiated cyclization of GGPP[
The oxidative metabolism of the products of cyclization of GGPP has only been studied in
detail for a few groups of diterpenes[ Details information on the soluble 1!oxoglutarate!dependent
dioxygenases is emerging from studies on gibberellin biosynthesis[ Characterization of the micro!
somal P349 oxidases however has been less tractable[
The progress that has been made sets the scene for the genetic engineering of diterpene biosynthesis
as a means of studying the regulation of pathways and ~ux of precursors into them and also to
manipulate diterpene synthesis to give desirable properties[ Uses may range from the production of
rare medicinal terpenes in amenable plants or microorganisms to the manipulation of plant devel!
opment by sense or antisense expression of gibberellin biosynthesis genes a goal that has already
been achieved in Arabidopsis or to the manipulation of the plant defense response via terpenoid
phytoalexins and antifeedant compounds[