Diversifying biosynthetic pathways in engineered cells

CHED 1586

Claudia Schmidt-Dannert, schmi232@tc.umn.edu, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 1479 Gortner Ave, St. Paul, MN 55108
Utilization of the biosynthetic machineries of microbial cells allows the production of complex chemical compounds that are otherwise inaccessible by chemical synthesis or isolation from natural sources. By mining genome sequences for biosynthetic genes and combining identified genes from different organisms into functional biosynthetic pathways, we can produce novel natural and unnatural compounds in recombinant cells. We use in vitro evolution and structure guided mutagenesis methods to alter catalytic functions of biosynthetic enzymes. This approach has been initially applied to the production of carotenoids in engineered cells. Gene combination together with directed evolution of enzyme functions resulted in the production of a diverse set of carotenoid structures. Mining of microbial genomes identified novel carotenoid biosynthetic genes, which when combined into our pathways resulted in the production of novel highly-polar carotenoid structures. More recently, we have created new biosynthetic pathways for the overproduction in E. coli of other compounds of interest as e.g. therapeutics, agrochemicals, nutraceuticals, chemical catalysts and novel conductive materials. For example, pathways have been engineered that allow the high-level production of diverse tetrapyrrole structures in E. coli. To access the structurally diverse group of medicinally important flavonoid compounds made by plants, we have engineered E. coli cells that allow the overproduction of diverse flavonoid structures.
 

Exploring and Exploiting Nature with Biomimetics
8:30 AM-11:45 AM, Tuesday, March 27, 2007 McCormick Place North -- Room N230A, Level 2, Oral

Division of Chemical Education

The 233rd ACS National Meeting, Chicago, IL, March 25-29, 2007