Polyketide engineering to supply advanced, complex scaffolds for the construction of high diversity, natural product-like combinatorial libraries

MEDI 540

Jasmina Nikodinovic, jasmina.nikodinovic@umontana.edu1, Bradley A. Bessette Jr.2, James E Cox2, Stephen C. Bergmeier, stephen.c.bergmeier@mail.promiliad.com2, Mark C. McMills2, Nigel D Priestley, nigel.priestley@umontana.edu1, and Dennis L Wright, dennis.l.wright@mail.promiliad.com2. (1) Department of Chemistry, University of Montana, Missoula, MT 59812-1656, (2) Promiliad Biopharma Inc, PO Box 10, Alberton, MT 59820-0010
The majority of pharmaceuticals are either natural products, are made from natural products or have structures that are inspired by natural products. Generating combinatorial libraries of compounds that have similar stereochemical and topological complexity to natural products is not straightforward. Such libraries, however, would sample regions of structural space not well covered by existing libraries. We have used a combination of genetic engineering, fermentation improvement and bioconversion to adapt the biosynthesis of the polyketide nonactin to generate a panel of stereochemically complex natural product building blocks ('bio-blocks') in scale and we have shown that these blocks can be used in the construction of complex, natural product-like compound libraries

 

General Poster Session
7:00 PM-9:00 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 11 September 2006 Moscone Center -- Hall D, Sci-Mix

Division of Medicinal Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006