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Abstract/Syllabus:
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5.451 Chemistry of Biomolecules I, Fall 2005. (Massachusetts Institute of Technology: MIT OpenCourseWare), http://ocw.mit.edu (Accessed 09 Jul, 2010). License: Creative Commons BY-NC-SA
Chemistry of Biomolecules I
Fall 2005
Crystal structure of shikimate kinase. (Image courtesy of the RCSB PDB. PDB ID: 1VIA. Badger, J., et al. "Structural analysis of a set of proteins resulting from a bacterial genomics project." Proteins 60 (2005): 787-796.)
Course Highlights
This course features a full set of problem sets with solutions in the assignments section.
Course Description
5.451 is a half-semester introduction to natural product biosynthetic pathways. The course covers the assembly of complex polyketide, peptide, terpene and alkaloid structures. Discussion topics include chemical and biochemical strategies used to elucidate natural product pathways.
Syllabus
The course is primarily based on recent scientific literature, but these books may provide helpful background.
Recommended Textbook
Dewick, Paul M. Medicinal Natural Products: A Biosynthetic Approach. 2nd ed. New York, NY: John Wiley & Sons, Inc., 2001. ISBN: 9780471496410 (paperback); ISBN: 9780471496403 (hardcover).
Optional Textbook
Silverman, Richard B. The Organic Chemistry of Enzyme-Catalyzed Reactions. San Diego, CA: Academic Press, 2002. ISBN: 9780126437317.
Grading
Grading criteria.
| ACTIVITIES |
PERCENTAGES |
| Homework 1 |
25% |
| Homework 2 |
25% |
| Homework 3 |
25% |
| Exam |
25% |
Academic Honesty
It is expected that students will maintain the highest standards of academic honesty.
With respect to homework assignments, it is expected that no student will turn in work that is not his or her own by copying the work of another student or by using the work or solutions from this course given in previous years. Discussion of approaches to solving the homework problems after attempting to work the problems independently, however, is permitted and encouraged.
It is expected that during a test or examination, a student will not:
- accept or use information of any kind from other students,
- represent the work of another student as his or her own,
- use aids to memory other than those expressly permitted by the examiner.
Following a test or examination, a student will not try to deceive teachers or graders by misrepresenting or altering his or her previous work. In advance of a test or exam, a student will not knowingly obtain access to the exam questions.
Departures from the above standards are contrary to fundamental principles of MIT and of the larger scientific community. Such departures are considered serious offenses for which disciplinary penalties, including suspension and expulsion, can be imposed.
Calendar
Course schedule.
| LEC # |
TOPICS |
KEY DATES |
| 1-2 |
Peptide Biosynthesis: Ribosomal and Non-Ribosomal |
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| 3-4 |
Polyketide Biosynthesis |
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| 5-6 |
Glycosylation and Halogenation |
Problem set 1 due on Lec #5 |
| 7-8 |
Shikimate Pathway |
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| 9-10 |
Alkaloid Biosynthesis |
Problem set 2 due on Lec #9
Problem set 3 due on Lec #10 |
| 11-12 |
Terpene Biosynthesis |
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Final Exam |
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Further Reading:
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Readings
Dewick readings are from the required textbook:
Dewick, Paul M. Medicinal Natural Products: A Biosynthetic Approach. 2nd ed. New York, NY: John Wiley & Sons, Inc., 2001. ISBN: 9780471496410 (paperback); ISBN: 9780471496403 (hardcover).
Course readings.
| TOPICS |
READINGS |
| Introduction and Peptide Biosynthesis |
Dewick, chapter 7, pp. 421-454.
Chatterjee, Champak, et al. "Biosynthesis and Mode of Action of Lantibiotics." Chem Rev 105 (2005): 633-683.
Sieber, Stephan A., and Mohamed A. Marahiel. "Molecular Mechanisms Underlying Nonribosomal Peptide Synthesis: Approaches to New Antibiotics." Chem Rev 105 (2005): 715-738. |
| Polyketide Biosynthesis |
Dewick, chapter 3, pp. 60-117.
McDaniel, Robert, Mark Welch, and C. Ricard Hutchinson. "Genetic Approaches to Polyketide Antibiotics 1." Chem Rev 105 (2005): 543-558.
Weissman, Kira J., et al. "The Molecular Basis of Celmer's Rules: The Stereochemistry of the Condensation Step in Chain Extension on the Erythromycin Polyketide Synthase." Biochemistry 36 (1997): 13849-13855.
Shen, Ben. "Polyketide biosynthesis beyond the type I, II and III polyketide synthase paradigms." Current Opinion in Chemical Biology 7 (2003): 285-295. |
| Glycosylation and Halogenation |
Dewick, chapter 8, pp. 465-485. |
| Aromatic Polyketide Biosynthesis |
Shen, Ben. "Biosynthesis of Aromatic Polyketides." Topics in Current Chemistry 209 (2000): 1-51. |
| Saccharide Biosynthesis |
He, Xuemei M., and Hung-wen Liu. "Formation Of Unusual Sugars: Mechanistic Studies and Biosynthetic Applications." Annu Rev Biochem 71 (2002): 701-54.
Koeller, Kathryn M., and Chi-Huey Wong. Fig. Schemes 2 and 5 in "Synthesis of Complex Carbohydrates and Glycoconjugates: Enzyme-Based and Programmable One-Pot Strategies." Chem Rev 100 (2000): 4465-4494.
Walsh, Christopher. Enzymatic Reaction Mechanisms. San Francisco, CA: W.H. Freeman Company, 1978, pp. 778-781. ISBN: 9780716700708.
He, Xuemei, Gautam Agnihotri, and Hung-wen Liu. Structures 3-6, Scheme 2, and Scheme 1 in "Novel Enzymatic Mechanisms in Carbohydrate Metabolism." Chem Rev 100 (2000): 4615-4662.
He, Xuemei, and Hung-wen Liu. Schemes 5, 6, 7, 8, 9, 11, 14, 16, and 17 in "Formation Of Unusual Sugars: Mechanistic Studies and Biosynthetic Applications." Ann Rev Biochem 71 (2002): 701-754.
Chen, Huawei, et al. Scheme 1 in "Deoxysugars in glycopeptide antibiotics: Enzymatic synthesis of TDP-L-epivancosamine in chloroeremomycin biosynthesis." PNAS 97 (2000): 11942-11947. |
| Shikimic Acid |
Dewick, chapter 4, pp. 121-132, 142-144, and 149-157.
Mann, John. "The shikimic acid pathway: biosynthesis of phenols, lignans, flavonoids, etc." In Chemical Aspects of Biosynthesis. New York, NY: Oxford University Press, 1995, pp. 53-7. ISBN: 9780198556763.
Choroba, Oliver W., Dudley H. Williams, and Jonathan B. Spencer. "Biosynthesis of the Vancomycin Group of Antibiotics: Involvement of an Unusual Dioxygenase in the Pathway to (S)-4-Hydroxyphenylglycine." J Am Chem Soc 122 (2000): 5389-5390.
Austin, Michael B., and Joseph P. Noel. "The chalcone synthase superfamily of type III polyketide synthases." Nat Prod Rep 20 (2003): 79-110. |
| Alkaloids |
Dewick, chapter 6, pp. 291-337, 368-376, and 393-396. |
| Terpene Biosynthesis |
Dewick, chapter 5, pp. 167-186, and 191-219.
Davis, Edward M., and Rodney Croteau. "Cyclization Enzymes in the Biosynthesis of Monoterpenes, Sesquiterpenes, and Diterpenes." Topics in Current Chemistry 209 (2000): 53-95.
Carey, Francis A., and Richard J. Sundberg. Advanced Organic Chemistry, Part A: Structure and Mechanisms. New York, NY: Springer-Verlag, 2004, pp. 312-9. ISBN: 9780306462436.
Hayes, T., et al. "Feminization of male frogs in the wild." Nature 419 (2002): 895-6.
Peters, Reuben J., et al. "Bifunctional Abietadiene Synthase: Mutual Structural Dependence of the Active Sites for Protonation-Initiated and Ionization-Initiated Cyclizations." Biochemistry 42 (2003): 2700-2707.
Ye, Xudong, et al. "Engineering the Provitamin A (β-Carotene) Biosynthetic Pathway into (Carotenoid-Free) Rice Endosperm." Science 287 (2000): 304-5.
Jennewein, Stefan, et al. "Random sequencing of an induced Taxus cell cDNA library for identification of clones involved in Taxol biosynthesis." PNAS 101 (2004): 9149-9154.
Williams, David C., et al. "Intramolecular proton transfer in the cyclization of geranylgeranyl diphosphate to the taxadiene precursor of taxol catalyzed by recombinant taxadiene synthase." Chemistry & Biology 7 (2002): 969-977. |
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