Benzophenone metabolism yields complex constituents, which constitute the class of polyprenylated polycyclic acylphloroglucinols (PPAPs). Approximately 1000 PPAPs have been isolated and structure elucidated. They are either bridged bicyclic ring systems or tri- and tetracyclic compounds with caged skeletons. Many PPAPs possess interesting pharmacological activities, such as antitumoral, antibacterial and antiviral properties. However, their concentrations in plants (primarily Hypericaceae and Clusiaceae) are low, which limits their pharmaceutical development and stimulates biotechnological approaches.
The skeleton of benzophenones originates from benzoyl-CoA and three molecules of malonyl-CoA, catalyzed by benzophenone synthase. A point mutation in this type III polyketide synthase opens a new pocket in the active site cavity and transforms the enzyme into phenylpyrone synthase.
Besides glycosylation and dimerization, simple benzophenones can undergo stepwise prenylations with C5 and C10 side chains and concomitant cyclizations, resulting in PPAPs. The prenyltransferases involved are under study. They are integral membrane proteins, which are located in the envelope of chloroplasts.
Alternatively, regioselective oxidative phenol couplings lead to formation of two isomeric xanthones, which are the precursors of all plant xanthones. This class of constituents also includes many complex metabolites with pharmacological activities. The intramolecular cyclizations are catalyzed by bifunctional cytochrome P450 enzymes, which belong to the new CYP81AA subfamily. The two enzymes catalyze identical 3' hydroxylations but subsequently alternative regioselective ring closures. A sextuple mutation in the active site interconverted the functions of the enzymes. At the level of xanthones, there are also prenylation reactions; for example, sequential regiospecific gem-diprenylation was detected.
