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. ? ? ?
| Crawford, Jason M; Thomas, Paul M; Scheerer, Jonathan R et al. (2008) Deconstruction of iterative multidomain polyketide synthase function. Science 320:243-6 |
