ORGN 234 |
| Thousands of polyketide and nonribosomal peptide natural products are assembled on multimodular enzymatic assembly lines. Natural product acyl chains grow as a series of thioester intermediates covalently tethered via phosphoantetheinyl arms to carrier protein domains, with initiation, elongation, and termination steps. Tailoring enzymes can act during chain growth on the assembly lines or in post assembly line modifications. Two on-assembly line tailoring processes that diversify natural product scaffolds are: (1) introduction of beta branching in polyketides, and (2) depsipeptide formation in nonribosomal peptides by alpha-hydroxy acid instead of alpha-amino acid monomers to make ester rather than amide bonds. The polyketide beta branching arises by convergence of isoprenoid and polyketide enzymatic assembly line machinery while the ester linkages in NRPs such as valinomycin and cereulide arise by in situ reductions of tethered alpha-keto acid monomers. |
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Nakanishi Prize: Symposium in Honor of Hung-wen Liu
8:15 AM-12:05 PM, Monday, March 26, 2007 McCormick Place Lakeside -- Room E451A/B, Level 4, Oral
Division of Organic Chemistry |