A Bioorganic View of Biosynthesis
 
Topics:
Fatty acid biosynthesis.
Terpene biosynthesis
Isotopic labeling and tracing
Squlene cyclization.  
Biomimetic polyene cyclization.
Reengineering Polyketide synthases.
Non-Ribosomal Peptide Synthesis
 
Self-Study Questions:
 
1.  How is ATP used to drive fatty acid biosynthesis, terpene biosynthesis, and non-ribosomal peptide synthesis.
2.  How can radio-labeling as well as single and double isotopic labeling be used elucidate the biosynthetic origin of natural products?
3.  What aspects of squalene cyclization reactions can be mimicked non-enzymatically?  
What aspects of squalene cyclization reactions can NOT be mimicked non-enzymatically?
4.  What non-covalent interactions do “terpene cyclases” provide to catalyze these reactions?  (What amino acids are used)
5.  How can genes be manipulated through deletion, insertion or N-terminal/C-terminal modification of genes involved in polyketide synthesis.
What are the similarities/differences between PKS’s and NRPS’s?
 
Download (PDF) The Lecture: Discussion Paper of the Week:
Required Reading: Recent developments towards the heterologous expression of complex bacterial natural product biosynthetic pathways Current Opinion in Biotechnology 2005, 16, 594-606. http://www.udel.edu/chem/koh/LG11/heterologousbiosynth.pdfshapeimage_4_link_0
References: PKS engineering: Tolerance and Specificity of Polyketide Synthases, C. Khosla, R. Gokhale, J. Jacobsen, D. Cane. Annu Rev. Biochem. 1999 219-253 *K. Ulrich, G. Schultz, E.J. Corey, D. R. Liu, Enzymatic Mechanisms for Polycyclic Triterpene Formation, Angew. Chem. Int. Ed., 2000, 39, 2812-2833. (Available on line) *L. Katz Manipulation of Modular Polyketide Synthases, Chem. Rev., 1997, 97, 2557-2575. (Available on line) (There are several other excellent reviews in this special issue of Chemical Reviews dedicated to biosynthesis of natural products.) M. Marahiel, T. Stachelhaus, H. Mootz; “ Modular Peptide Synthetases Involved in Nonribosomal Peptide Synthesis”, Chem. Rev., 1997, 97, 2651-2673. Classic Refs to secondary metabolism: J. Mann, Seconday Metabolism, 2nd Ed, 1987 Oxford Science Publications (The third edition of this book has recently come out) There are a series of old but excellent review published in: Comprehensive Organic Chemistry; Volume 5; Biological Compounds, Sir Derek Barton, W. David Ollis Eds, 1979, Pergemon Press, Oxford. (In reference section QD 245.C65) (Well worth a quick flip through – It is amazing how much work has been done in this area, even up to 1979!) http://www.udel.edu/chem/koh/LG11/KhoslaAnnRev.pdfshapeimage_5_link_0