Identifying new enzyme catalysts for complete biosynthesis of anticancer drug vinblastine

This project focuses on identifying novel enzyme catalysts to complete the biosynthesis of vinblastine, a potent anticancer alkaloid, by sourcing them from diverse plant species that produce dimeric indole alkaloids similar to vinblastine. Vinblastine, a member of the monoterpenoid indole alkaloid (MIA) family, is naturally derived from Catharanthus roseus. While its biosynthetic pathway, consisting of over 30 enzymatic steps, has been extensively studied, several key steps remain unresolved, limiting the feasibility of fully reconstructing its biosynthesis in heterologous systems.

The primary objective of this research is to screen and biochemically characterize novel enzyme catalysts from multiple species within the Gentianales order to evaluate their potential for completing vinblastine biosynthesis. This involves identifying and testing enzymes with enhanced efficiency, specificity, expression, and stability from a curated candidate gene dataset. Additionally, metabolomic analysis will be conducted on both in vitro and in vivo enzyme products to verify and evaluate tandem enzymatic catalysis for vinblastine biosynthesis.

By leveraging the combined expertise in plant specialized metabolism, biochemistry, and enzyme/pathway engineering from two collaborating labs, this 24-week Mitacs Globalink project aims to discover key enzyme catalysts that will advance the total biosynthesis of vinblastine.

Faculty Supervisor:

Yang Qu

Student:

Partner:

Zhejiang University

Discipline:

Life Sciences

Sector:

Education

University:

University of New Brunswick

Program: