2. Learning Outcomes for the Module:  to build an understanding of the reasons why organisms make so many different chemicals  to give an appreciation of the way theories arise and fall  to show how ideas can be drawn together from different areas of biology to give a bigger, better picture of the way organisms work  to illustrate the economic, social and historical importance of Natural Products  to change the way you see the world

3. Learning Outcomes for Lecture 1 At the end of this lecture you should:  be aware of the web pages that support the moduleweb pages  have noted a "route map" for the remainder of this module  appreciate what we mean by Natural Products - NPs  be familiar with the kinds of organisms that make NPs  appreciate why many NPs are different from synthetic products (= human made) in structural terms  know why a microbe easily make a chemical that a chemist finds very hard to make  realise that there are only a few major classes of NP classes made by plants and microbes

4. Natural Products and natural products – they are different

5. Lecture 1.What are NPs? Where do you find them? Lecture 2.The commercial importance of NPs Lecture 3.Explanations of why organisms make NPs Lecture 4.The Screening Hypothesis Lecture 5.The evidence for and against this theory Lecture 6.The Implications of the Screening Hypothesis - Ecotoxicology & Bioremediation Lecture 7.The Implications of the Screening Hypothesis - GM & Bioprospecting Lecture 8.The Implications of the Screening Hypothesis - Plant/insect and plant/fungal interactions Lecture 9.Where next

6. Natural Product - how did the term arise? 1769-85Scheele showed that tartaric acid in grapes, citric acid in lemons, malic acid in apples, gallic acid in galls, lactic acid in milk, uric acid in urine. 1772-7 Lavoisier burned sugar, ethanol and acetic acid in oxygen and found only CO 2 and H 2 O, thus the burned chemicals must have been made of carbon and hydrogen only. Quantification showed that they must also contain oxygen. Later studies by others found that some natural substances when burned also gave off nitrogen hence must also contain nitrogen. 1807 Berzelius introduced the terms organic and inorganic, to refer to chemicals made by living organisms and found in minerals respectively

7. Natural Product - how did the term arise? 1828 Wöhler showed that he could make urea hence the “vital force” of living organisms was not needed to make organic chemicals. 1833 Persoz and Payen first noted enzyme activity. The concept of vitalism now transferred to enzymes in whole cells. However in 1897 Büchner showed enzyme activity in cell-free solutions so vitalism suffered a final blow. 19th C. The blossoming of the study of organic molecules gradually split into the study of man-made organic chemicals (the organic chemicals and organic chemistry of today) and organic chemicals made by organisms (=Natural Products and Natural Product Chemistry of today).

8. Natural Product - how did the term arise? 19th C. “Physiological chemistry” was the study of enzymes and the chemistry in organisms. 1891 Kössel, a German physiological chemist, proposed that the metabolism of organisms could be divided into two type. Primary metabolism was the basic biochemistry common to all cells. Secondary metabolism was the type of biochemistry found only in some species. Thus to physiological chemists, later to be called biochemists, Secondary Metabolites are what chemists call Natural Products. 20th C Physiological chemistry split off from Chemistry Departments and became Biochemistry... but that split normally left Natural Products being studied in Chemistry Departments and now ignored by biochemists. None of the major introductory biochemistry texts in the library give the term Natural Product in their indices!

9. Natural Product - how did the term arise?

10. Are synthetic chemicals different from natural ones? Synthetic chemicals are made by the use of chemically reactive reagents. The chemicals tend to fairly crude in bring about changes to structures – addition, subtraction, substitution and rearrangements Natural Products are made by enzymes which can be much more selective – they can target their action on parts of the molecule by bringing the active site of the enzyme into close proximity with one part of the molecule to be changed

11. Are synthetic chemicals different from natural ones?

12. The basic shape of Natural Product Metabolism

13.  Shikimate derived - the phenylpropanoids [C6-C3-C6]  Mevalonate derived - the terpenoids [C5 multiples]  Acetate derived - the polyketides  The alkaloids [Nitrogen containing]

14. The great chemists?