Biosynthesis of Unnatural Flavonoids in Recombinant Microorganisms

 

Joseph Chemler and Ryan Lim

 

Flavonoids are a large class of plant secondary metabolites that are involved in the beneficial effects diets rich in fruits and vegetables have in human health. The overall goal of our work is the biosynthesis of novel flavonoid molecules using genetically tractable microbial species, such as Escherichia coli and Saccharomyces cerevisiae (yeast). This is achieved through episomal introduction of the flavonoid metabolic circuits from various plant species in these organisms. Using these constructed recombinant strains, mutasynthesis allows the production of novel, unnatural flavonoid analogues with different substitutions on the flavonoid core structure consisting of hydroxyl, fluoro and amino groups. By expressing different combinations of flavonoid enzymes in each recombinant strain, a number of flavonoid subclasses have been synthesized including flavanones, 5-deoxyflavonones, flavones, dihydroflavonols, leucoanthocyanidins and anthocyanidins [Chemler, et al. 2007]. A library of over 25 novel, unnatural flavonoids has been made and continues to expand by extending the flavonoid pathway. We are currently investigating the use of some of the synthesized compounds for diabetes and obesity treatments. We are also testing these compounds for their effect in increasing insulin secretion in pancreatic beta cells as well as their application as anti-obesity agents.
 

Figure: Unnatural flavonoids biosynthesized in S. cerevisiae and E. coli.