Plants and their diverse specialized metabolites have been used by humans for centuries in traditional and modern medicine. They remain an important source for the discovery of new pharmaceuticals and nutraceuticals. Montbretin A (MbA) is a complex flavonoid metabolite; a highly potent and selective inhibitor of the human pancreatic α-amylase (HPA); and a potential new treatment option for Type-II diabetes and obesity. The only known source for MbA are the below-ground storage organs of montbretia (Crocosmia) species, which are native to the grasslands of southern and eastern Africa and commonly grown in gardens around the world.

Due to the low abundance of MbA in montbretia and due its complex chemical structure, natural product extraction and chemical synthesis are insufficient for scalable MbA production. Our goal is to develop an improved bio-production system for MbA using genes, enzymes and regulating factors of MbA biosynthesis in montbretia. In recent work, we discovered the complete biosynthetic pathway of MbA using an approach that combined knowledge of montbretia biology, metabolite profiling, differential transcriptome analysis, cDNA cloning, heterologous gene expression, and enzyme biochemistry.

This includes the discovery of genes encoding UDP-sugar dependent glycosyltransferase and acyltransferase enzymes, which catalyze the assembly of MbA from its different building blocks. We are using these genes to bioengineer the production of MbA in yeast and plants. This presentation will discuss challenges and opportunities of exploring plant biosynthetic systems for the development of new drugs, and bioproducts in general.