The genetic manipulation of Natural Product composition - risk assessment when a system is predictably unpredictable.
R D Firn
In Epigenetics, Transgenic Plants and Risk Assessments (2006) Edited by Katya Moch, Oeko Institute. A pdf copy of the volume can be downloaded. Note that this link takes you to a search page where you can type “epigenetics” into the title box then search. The book by Moch M (2006) is the one that contains the article and many other interesting one.
If a biologist looks at an ecosystem, an organism, a cell or an organelle they can usually see some patterns or order that fits within a larger evolutionary framework and they can use that framework to interpret what they are seeing. Yet if a biologist is shown a map of all known biochemical pathways they are unlikely to see any patterns - it is just a collection of names and arrows. So why is biochemistry shaped like it is? How does selection work at the pathway level? In attempting to answer these questions it has become apparent that too much attention has been paid to the evolution of individual enzymes and not enough attention has been paid to the products these enzymes make. Not all chemicals made by cells serve the same type of role hence selection pressures on enzymes vary depending on the role of the product being made. Once one appreciates this proposition a more holistic view of biochemistry comes into focus and some old dogmas can be seen to be at best simplistic and at worst misleading. Every biochemistry textbook emphasises that enzymes are highly substrate specific or that all enzymes can only make one product yet this is simply not true. For example in the pathways leading to Natural Products evolution has selected enzymes with broad substrate tolerances because that enhances the production, and retention, of chemical diversity. There are now many examples of enzymes that can act on multiple substrates to make different products and even some examples of enzymes that make multiple products from one substrate. Such metabolic flexibility explains why you can buy so many different types of mint in the garden centre, why scented leaf pelagoniums can smell of orange, peppermint, cedar, rose or apple and why there are many destinctive flavours of apple. However, this variation in odour, which we accept so readily, is revealing a diversity of molecules with only one property (able to interact with human olfaction receptors) yet there is evidence that such variation is a feature common to all classes of Natural Product. The new evolutionary model outlined suggests that the genetic manipulation of certain types biochemical pathways will have a reasonably predictable outcomes but other pathways if extended or changed will produce highly unpredictable, and sometimes hard to discover, effects. The model also provides a new perspective on the concept of “substantial equivalence”.