The planned research described in this proposal targets the biosynthesis of enediyne antibiotic natural products, in particular the 10-membered class as represented by calicheamicin. The primary objective is the exploration of flexible and efficient synthetic routes to proposed intermediates on the biosynthetic pathway and investigation of intrinsic biomimetic chemistry. Proteins involved in the biosynthesis will be expressed and these potential intermediates will be tested as their CoA or N-acetylcysteamine thioesters. Isotopic labeling and feeding studies will parallel synthetic progress.
The research aims to provide valuable and specific chemical and structural information that is complementary to recent genetic advances made toward the biosynthesis of enediyne antibiotics. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM079408-03
Application #
7488385
Study Section
Special Emphasis Panel (ZRG1-F04A-D (20))
Program Officer
Fabian, Miles
Project Start
2006-09-01
Project End
2009-07-31
Budget Start
2008-09-01
Budget End
2009-07-31
Support Year
3
Fiscal Year
2008
Total Cost
$45,313
Indirect Cost
Name
Johns Hopkins University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Crawford, Jason M; Thomas, Paul M; Scheerer, Jonathan R et al. (2008) Deconstruction of iterative multidomain polyketide synthase function. Science 320:243-6