Transcript Lecture 1. What are Natural Products (NPs)?

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
Learning Outcomes for Lecture 1
At the end of this lecture you should:
 be aware of the web pages that support the module
 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
Natural Products and natural products
– they are different
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
Natural Product - how did the term
arise? Scheele showed that tartaric acid in grapes, citric
1769-85
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 CO2 and H2O, 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
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).
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!
Natural Product - how did the term
arise?
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
Are synthetic chemicals different from natural ones?
Paramet er
Trade drugs
Nat ural Product s
(From Man-Ling Lee & G Schneider, 2001)
Collect ion size
5,757
Average molecular w eight
10,495
356 (261)
Log Pc (est imat e of f at solubilit y) 2.1 (3)
360 (166)
2.9 (3)
H donors per molecule
2.5
1.8
N at oms per molecule
2.3
1.4
O at oms per molecule
4.1
4.3
“ Rule-of -5” alert s (see box)
10%
12%
(Numbers in parent hesis are St andard Deviat ions )
The basic shape of Natural Product Metabolism
The basic shape of Natural Product Metabolism
 Shikimate derived - the
phenylpropanoids [C6-C3-C6]
 Mevalonate derived - the
terpenoids [C5 multiples]
 Acetate derived - the
polyketides
 The alkaloids [Nitrogen
containing]
The great chemists?