ORGN 615 |
| A. Ian Scott, Department of Chemistry, Department of Chemistry, Texas A&M, P.O. Box 30012, College Station, TX 77842-3012 |
| Biosynthetic pathways to natural products frequently involve ten or more discrete enzyme-catalyzed steps. While administration of precursors labeled with radio- (14C, 3H) and stable (13C, 15N, 2H) isotopes has provided a great deal of information on the biosynthetic routes involved, the many metabolic branches operating in living cells frequently reduce the overall yield of precursor incorporation of 1-5% or less. In this lecture, we discuss the application of recombinant DNA techniques to overexpress the biosynthetic enzymes necessary to reach the target of interest, together with the development of high resolution NMR techniques to assay each synthetic step and, in some cases, to study the enzyme mechanism. The feasibility of harnessing the complete repertoire of as many as 10 or 15 enzymes to achieve the one-flask total synthesis of a rare natural product of biological importance will be addressed. The synthetic targets include anti-tumor alkaloids, antibiotics, steroids and vitamins, all of which contain a wealth of stereochemical complexity in their structures and frequently involve unstable intermediates in their biosynthesis. Finally, a new concept of adapting the genetic machinery for protein synthesis to the formation of carbon-carbon bonds via misacylation of t-RNA will be advanced. |
|
Nakanishi Prize
2:00 PM-4:40 PM, Wednesday, March 26, 2003 Convention Center -- La Nouvelle Ballroom A/B, Oral
Division of Organic Chemistry |