Natural Product Biosynthesis (303J)
Dr J M Sanderson, Ext 42107, Room CG112.
for further information.
These lectures provide knowledge of the mechanisms used by living
organisms to synthesise a range of complex organic molecules, and will highlight the mechanistic aspects
of key reactions in these biosyntheses.
By the end of these
lectures, students should be able to:
- Explain the difference between primary and secondary metabolites.
- Outline the principal metabolic pathways
(glycolysis, carboxylic acid cycle, pentose phosphate pathway, fatty acid
biosynthesis), including a diagrammatic representation of the relationship between
them and the chemical structures of key primary metabolites (glucose-6-phosphate, phosphoenol pyruvate,
acetyl CoA, mevalonate).
- Describe, with detailed examples, how isotope
labelling and NMR spectroscopy may be used to elucidate biosynthetic pathways.
- Demonstrate an understanding of the chemical strategies
used in the biosynthesis of 2° metabolites and
the role of cofactors in performing biochemical transformations.
- Given their structures, describe the biosynthesis of important biosynthetic
intermediates (e.g. malonyl CoA, chorismate, geranyl pyrophosphate, cadeverine/putrescine/tryptamine/tyramine)
from a 1° metabolite, with reference to the enzymes involved and mechanistic details of the key steps.
- Propose a feasible route to a 2° metabolite consistent with observed labelling patterns in feeding
experiments using labelled nutrients.
- Identify the metabolic pathways involved in the biosynthesis of a 2° metabolite, given its structure.
- Compare and contrast non-ribosomal peptide synthesis and polyketide synthesis.
Lecture 1: Introduction.
The biochemical environment. The roles of enzymes and cofactors in biocatalysis.
Overview of major metabolic pathways. Definition of a 2° metabolite.
Methods for studying important biosynthetic reactions. Polyketide biosynthesis.
Biosynthesis of polyketides (contd.).
Synthase. The module hypothesis. Non-ribosomal peptide synthesis.
The Shikimate pathway. Chorismate Mutase.
The isoprene repeating unit. Biosynthesis of terpenes and steroids.
Biosynthesis of alkaloids.
Biosynthesis of alkaloids (contd.). Course overview.
J. M. Berg, J. L. Tymoczko and L. Stryer, "Biochemistry", W. H. Freeman &
Co., 7th ed.,
J. Clayden, N.
Greeves, S. Warren and P Wothers, "Organic Chemistry", Oxford University Press,
P. Y. Bruice,
"Organic Chemistry", Prentice Hall, 5th ed.,
More Specific Texts:
J. R. Hanson,
“Natural Products: the Secondary Metabolites”, RSC,
J. Mann, "Chemical Aspects of Biosynthesis", OUP,
§ essential reading