S15: Discovery and design of terpenoid biosynthetic pathways

Isoprenoids represent a large class and diverse group of natural products with many important biological functions. Engineering of isoprenoid pathways into microbial cells allows synthesis of isoprenoid compounds that may otherwise be inaccessible by chemical synthesis or isolation from natural sources. Combination of biosynthetic genes isolated from different organisms into functional pathway allows the production of diverse isoprenoid compounds in recombinant cells. In vitro evolution and/or structure guided mutagenesis of biosynthetic enzymes creates new biosynthetic activities for the synthesis of novel compounds. Using these strategies we have introduced pathways into E. coli for the biosynthesis of diverse carotenoids, apocarotenoids and ubiquinones with desaturated prenyl-chains. More recently we have shifted our focus towards the discovery and characterization of sesquiterpene biosynthetic pathways in bacteria and higher fungi. Our studies show that higher fungi (basidiomycetes) are a rich source for the discovery of novel, bioactive sesquiterpene pathways.