Mid-Term Report Summary - SYNPLANTMET (Synthetic Metabolism in Plants: Elucidating Vinblastine Biosynthesis and Implementing Strategies to Overproduce Complex Plant Metabolites)
My research group discovers how plants make pharmacologically important medicinal compounds. If we discover the genes that make these products, then we can use these genes to rebuild the pathway in a new, convenient host system. This would allow inexpensive production of the compound, and also provides the opportunity to engineer the pathways to make new derivatives of these compounds that may have improved or novel bioactivity. Through this grant, my group has discovered numerous missing genes that encode the pathways for pharmacologically important compounds in the medicinal plant Catharanthus roseus. A number of these have been published in the last year. Transcriptome data, as well as the recently sequenced genome of this plant that my group coordinated, was used to make these discoveries. We have now used these newly discovered genes to produce pharmacologically active compounds in baker’s yeast. Specifically, we have successfully reconstituted the compound strictosidine, which is the precursor to many pharmacologically active compounds. This is one of the longest pathways to be reconstituted in yeast to date (ca. 21 genes). We are continuing this work by 1) discovering more missing genes that are involved in production of pharmacologically important compounds; 2) integrating these new genes into our yeast host to make more compounds and; 3) continuing to optimize the yeast host to increase the yields of these compounds.