The Genetic Manipulation of NPs

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Lecture 8 The Genetic Manipulation of NPs
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• Learning Outcomes
• Genetic manipulation of NP metabolism
• Why one might want to manipulate NPs
  composition?
• What could occur if you try to manipulate NP
  pathways?
• The concept of Equivalence does it help?
• The value of Metabolomics will it help
• The good, the bad and the ugly

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Why might you want to alter NP composition?

• increase yield of endogenous NP
• change relative of NPs
• produce new, higher value, products by
  introducing an exotic NP
• reduce costs, maybe by processing
• reduce losses due to
• insects some NPs might help?
• fungi some NPs might help?
• weeds some NPs might help?
• viruses some NPs might help?
• bacteria some NPs might help?

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Genetic manipulation of NP Metabolism we get
into the old arguments that have hindered the
adoption of GM crops in Europe and cause concern
elsewhere There can be no hard and fast rules
GM is safe or GM is dangerous are both gross
oversimplifications.
Safe for which organism?
Safe under which conditions?
We can never prove anything is safe, we can only
give a statistical evaluation of risk.
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Genetic manipulation of NP Metabolism are NPs
different?
The addition of a gene to an organism simply adds
the capacity to make a new protein it is the
properties of the protein that matter. Proteins
possess different properties.
Addition of a gene coding for a new protein,
which is simply a toxin, like the Bt toxin, will
change the plant in a fairly predictable way. The
plant will be identical except for containing Bt
protein?
Note that the addition of the Bt gene could have
predictable and unpredictable ecological
consequences.
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Old paradigm
New paradigm
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Genetic manipulation of NP Metabolism. Genetic
manipulation of NP Metabolism are NPs different?
What about the consequences of introducing an
enzyme?
The SH model suggests that the introduction of a
gene coding for a protein that is an enzyme
involved in NP metabolism will produce an
uncertain outcome. It is possible that more than
one new product will be made by the plant or
microbe (due to its broad substrate
tolerance). Furthermore, the existing NP
metabolism enzymes in the pathway may make yet
more chemical diversity
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Old paradigm
New paradigm
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Phenylpropanoid pathway
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Genetic manipulation of NP Metabolism.
Not everyone accepts this analysis T M Kutchan
(2005) Trends in Biotech. 23, 381 how are
metabolic pathways affected upon introduction of
a transgene? plants can be tailored in a
rational manner with marginal inadvertent
effects. This is an exciting milestone along
the way to general public acceptance of
genetically modified plants But others are
exploiting exactly the flexibility that the SH
predicts Polyketide pathway
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Genetic manipulation of NP Metabolism -
polyketides.
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Genetic manipulation of NP Metabolism -
polyketides.
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Genetic manipulation of NP Metabolism -
Polyketides
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Genetic manipulation of NP Metabolism -
Polyketides.
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Genetic manipulation of NP Metabolism
-polyketides.
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Genetic manipulation of NP Metabolism
-polyketides.
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Genetic manipulation of NP Metabolism. Equivalen
ce and Testing enough to avoid problems?
Equivalence bread flour in normal and Bt wheat
fairly easy to judge
Equivalence is a spearmint plant equivalent to
a peppermint?
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Analytical Testing metabolomics

• look for which chemicals?

• at what sensitivity?

• under what growing conditions?

• after which challenges?

• do we know enough about the toxicological
  properties of the many NPs found

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Genetic manipulation of NP Metabolism Summary

• NP metabolism has evolved to be flexible and
  unpredictable.
• The manipulation of NP metabolism will be
  possible but the outcomes will inevitably be
  unpredictable.
• Because NP are involved in organism
  interactions, and because such interactions are
  poorly understood, caution might be wise.
• But the good news is that most unplanned, weird
  new NPs that arise through GM will have a low
  probability of possessing biomolecular activity.