The seco-iridoid pathway from Catharanthus roseus.

Area of Science:

• Plant biochemistry and molecular biology
• Metabolic engineering and synthetic biology

Background:

• (Seco)iridoids and monoterpenoid indole alkaloids (MIAs) are plant-derived compounds with significant pharmacological and insect-repellent properties.
• Key MIAs like vinblastine and vincristine, used in cancer therapy, are produced at very low levels in Catharanthus roseus, limiting availability and increasing cost.
• A lack of complete knowledge regarding their biosynthesis pathways hinders efficient biotechnological production.

Purpose of the Study:

• To elucidate the complete biosynthesis pathway of (seco)iridoids and identify the missing enzymatic steps.
• To enable the heterologous production of complex MIAs in an alternative plant host.
• To validate the functionality of the identified enzymes for synthetic biology applications.

Main Methods:

• Identified and characterized the final four missing enzymes in the (seco)iridoid biosynthesis pathway.
• Engineered an alternative plant host by expressing eight genes from the (seco)iridoid pathway, two precursor-boosting genes, and two downstream alkaloid biosynthesis genes.
• Confirmed the successful heterologous production of the MIA strictosidine.

Main Results:

• The last four missing steps of the (seco)iridoid biosynthesis pathway were discovered.
• Heterologous expression of the complete pathway in a plant host enabled the production of strictosidine.
• The functionality of all enzymes involved in the pathway was confirmed.

Conclusions:

• The elucidation of the complete (seco)iridoid pathway provides crucial insights for metabolic engineering.
• The successful heterologous production of strictosidine demonstrates the utility of these enzymes for synthetic biology.
• This research paves the way for sustainable biotechnological production of valuable (seco)iridoids and MIAs for pharmaceutical and agricultural applications.