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Background  The terpenoid indole alkaloid (TIA) pathway leads to the production of pharmaceutically important drugs, such as the anticancer compounds vinblastine and vincristine. Unfortunately, these drugs are produced in trace amounts, causing them to be very costly. To increase production of these drugs, an improved understanding of the TIA regulatory pathway is needed. Towards this end, transgenic  Catharanthus roseus  hairy roots that overexpress the  ORCA2  TIA transcriptional activator were generated and characterized.    Results  Transcriptional profiling experiments revealed that overexpression of  ORCA2  results in altered expression of key genes from the indole and terpenoid pathways, which produce precursors for the TIA pathway, and from the TIA pathway itself. In addition, metabolite-profiling experiments revealed that overexpression of  ORCA2  significantly affects the levels of several TIA metabolites.  ORCA2  overexpression also causes significant increases in transcript levels of several TIA regulators, including TIA transcriptional repressors.    Conclusions  Results presented here indicate that ORCA2 plays a critical role in regulation of TIA metabolism. ORCA2 regulates expression of key genes from both feeder pathways, as well as the genes ( STR  and  SGD ) encoding the enzymes that catalyze the first two steps in TIA biosynthesis. ORCA2 may play an especially important role in regulation of the downstream branches of the TIA pathway, as it regulates four out of five genes characterized from this part of the pathway. Regulation of TIA transcriptional repressors by ORCA2 may provide a mechanism whereby increases in TIA metabolite levels in response to external stimuli are transient and limited in magnitude.

The ORCA2 transcription factor plays a key role in regulation of the terpenoid indole alkaloid pathway