The role of tryptophan as a biosynthetic precursor of indole-diterpenoid fungal metabolites: continuing a debate.

Studies in the 1980s and 1990s on the origin of the indole moiety in fungal indole-diterpenoids using (14)C-labelled tryptophan consistently showed autoradiographic evidence but gave low % incorporation of the probe. Recent studies on a member of the group (nodulisporic acid A), using more specific (13)C methodology, demonstrated a role of the tryptophan biosynthetic pathway but, in failing to show involvement of end-product, concluded that the indole was derived from indole-3-glycerol phosphate and suggested that the previous (14)C data arose via metabolic scrambling of label. In considering the protocol for the (13)C studies, there is concern that the fungal material was starved of an exogenous nitrogen source and thus could have degraded added labelled tryptophan. Consequently, synthesis of the serine necessary for anabolic formation of tryptophan may have been constrained. It is suggested that (13)C studies on appropriate fungi early in the idiophase of submerged or surface fermentation should be made before the biosynthesis of indole-diterpenoids can become clearer.