Transcript Lecture 3. Past and current theories as to why

The many and changing
ideas to explain existence
and the chemical diversity
of
Natural Products
Is it all the result of
co-evolution?
1. Humans have seemingly been obsessed with
NPs. Discuss the biological issues that you
consider to be relevant to the analysis of that
obsession.
2. Natural scents, colours and flavours are of
great commercial importance. How easy has it
been for breeders to maipulate the content of
these valuable products? Is that expected to
change?
At the end of this lecture you should appreciate:
 why some natural phenomena encourage scientists to devise a great
many, diverse explanations
 what kinds of explanations were proposed to explain NP diversity and
why each proposal had strengths and weaknesses
 why academic compartmentation hindered thinking - those working
on NPs in microbes rarely spoke to those working on NPs in plants
 the currently accepted paradigm
Subject fragmentation
The fragmentation of the study of NPs
Microbiologists interested in antibiotics
Entomologists interested in plant-insect interactions
Plant pathologists interested in plant-fungal interactions
Plant biologists thinking about plant-plant interactions
Zoologists thinking about animal food preferences
Chemists thinking about NPs structures
Biochemists thinking about enzymes making NPs
Waste products?
Plants lack an excretion system so how do they get rid of waste?
Plants unlike animals make Natural Products.
So maybe Natural Products are made as a way of getting rid of waste?
Alkaloids could function as nitrogen waste products like urea in mammals.
But do microbes and plants make waste? Why would they? Why would
evolution come up with so many varied ways of doing it and keep changing the
routes?
Fortuitous.
There is no reason …. It is just chance .. Afterall look at “junk DNA”
… why must there be a reason for everything?
Popular with some microbiologist but what would the selective advantage
be to the producer?
Biochemists and chemists were happy with this idea because they were not
really that fussed about evolution.
But many biologists found this idea offensive. Costs without benefits are
rarely beneficial. Any exceptions?
Relics of previous specific uses
One famous microbiologist claimed that the potency of the antibiotics,
and the fact that so many acted via an inhibition of protein or RNA
synthesis, suggested that these chemicals were once used by bacteria
as regulators but the regulation methodology had become redundant
and these were relics.
Why would this relic remain and not others when billions of years have
passed. Why would animals have got rid of them but not plants?
Inventive metabolism
Zahner, a microbiologist, argued that Natural Product metabolism was
needed to try out new branches of biochemistry. Thus the actual NPs were
not important as such but the “testing” of new enzymes was handy.
How came some organisms manage without such “testing”? What are they
testing for?
Alkaloids could act as nitrogen storage resevoirs for use by the
plant in nitrogen limiting situations.
What about NPs that were not alkaloids?
What is wrong with storing nitrogen in proteins – seed storage proteins are
common and some plants even make odd amino acids to store N in a form that
is hard for other organisms to access
Secondary metabolites could serve as growth regulators.
Gross argued that there are so many weird processes going on in plants that
many new “hormones” were awaiting discovery and NPs would turn out to be
very important in this role.
But most plants share much of their physiology and developmental patterns
(variations on common themes not different themes) so why has evolution kept
changing the controlling chemicals. Do we need 500,000 new regulators?
Secondary metabolites may be used to help the plant maintain
ionic balance, especially when the roots take up ions from the
soil.
And microbes?
Why did evolution come up with so many variants?
Would NPs really help?
Not how it happens.
Chemical warfare (or more usefully chemical interactions
between organisms)
As Demain (1995) said:
•"It has always amazed me that the importance of chemical compounds in
ecological interactions between plant versus herbivore, insect versus insect,
and plant versus plant has been universally accepted, but the importance of
antimicrobials in microbial interactions has been almost universally denied"
Constituitive vs inducible chemicals
Phytoalexins
Plant – insect interactions … Fraenkel (1959)
Erlich, P.R. and P.H. Raven
1964. Butterflies and plants: a study in coevolution. Evolution 18:586-608
Looked at patterns of host-plant use by butterflies. Ex. Umbelliferae
(Apiaceae)/Swallowtail butterflies Proposed a 5 step process
1. Random genetic event – plant produces novel compound by chance
2. Novel compound renders plant less suitable host plant
3. Plant freed from herbivore pressure, can undergo evolutionary radiation in
new adaptive zone
4. Random genetic event – insect evolves resistance to compound
5. Able to exploit previously unavailable resource, adapted insect enters new
adaptive zone and undergoes its won evolutionary radiation
Janzen 1980 argues for more restricted definition. Change in one species, in
response to selection imposed by another species, followed by a change in
the second species in response to the change in the first. Coevolution is a
..“Volatile metabolites of
Lycopersicon species are of
interest because of their roles in
tomato flavour and in host
defense against arthropod
herbivores ..” (Colby et al.,
1998).
Plant – insect interactions
 Negative
 Deterrents
 Feeding
 Oviposition
 Toxins
 Positive
 Oviposition
 Feeding
 Parasitism enhancers
"In some scientific circles it is something of a sport
to theorize about function, often with the intent of
finding one overriding axiom true for all secondary
metabolism. Speculations range from the notion
that they are waste products or laboratory artefacts,
to the concept that they are neutral participants in
en evolutionary game, to ideas of chemical
weaponry and signalling."
Bennett, 1995