The proposed research seeks to combine techniques of metabolic engineering with those of directed enzyme evolution (termed 'molecular pathway breeding') for the protection of useful novel chemical compounds and materials in recombinant cells. This application seek so to expand this approach to the biosynthesis of yet other, even more complex novel chemical compounds-porphyrins-demanding the development of new screening and analytical tools. Porphyrins are a fascinating, structurally complex compound class of enormous significance and potential for a variety of applications in e.g. medicine, chemistry or material sciences. Mimicking natural breeding processes through gene assembly and in vitro evolution of only a few functionally diverse available microbial porphyrin biosynthetic genes will generate new pathways for unnatural porphyrins. The strategies and methods developed in this project can be readily applied to other metabolic pathways and provide new engineering tools for the discovery and production, in recombinant cells, of a kaleidoscope of diverse natural and non-natural compounds for a variety of applications. In particular, the developed high-throughput (HT) screening methods for the identification of synthesized small molecules in large cell libraries will be highly useful for other combinatorial approaches as well. The biosynthetically produced new porphyrin structures with various reactive functional groups will make valuable scaffolds for chemical modifications for the synthesis of additional porphyrin structures.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM065471-03
Application #
6680906
Study Section
Special Emphasis Panel (ZGM1-MBP-1 (01))
Program Officer
Jones, Warren
Project Start
2002-01-10
Project End
2005-12-31
Budget Start
2004-01-01
Budget End
2004-12-31
Support Year
3
Fiscal Year
2004
Total Cost
$166,956
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Biochemistry
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455