Secondary metabolism and the risks of GMOs


The potential problems of altering the chemical composition of crops were discussed in your Briefing1. One aspect of this debate relates to secondary metabolism, which is an attractive area to exploit because of the importance of such compounds in resistance, defence and product quality. In our view, the rules governing the evolution and role of secondary metabolites need to be discussed and understood in order to understand the risks associated with the genetic modification of crops.

We have previously proposed2,3 a model based on the well-known fact that potent, specific biological activity is a rare property for a molecule to possess. In this model, organisms with a rich secondary metabolism (most plants and many microbes) have gained fitness by possessing metabolic traits that enhance the production and retention of chemical diversity. Two such traits could be a broad substrate tolerance of some of the enzymes involved in secondary metabolism, and the utilization of matrix pathways.

Two examples from terpenoid metabolism illustrate the metabolic flexibility proposed. In spearmint (Mentha gracilis), a mutation caused an enzyme to produce a new product, but several other new compounds were also made, at least one of which was unpredictable4. In the grand fir (Abies grandis), two enzymes can make multiple products from a single substrate (one produces 52 and the other 34)5. If such metabolic properties exist in all organisms with a rich secondary metabolism, the introduction of a gene could potentially have quite unpredictable outcomes, as in the following examples.

First, the introduction of an enzyme expected to produce a single new chemical could also produce other new compounds owing to the substrate tolerance of existing enzymes. Second, the introduction into a new organism of a gene encoding an enzyme involved in secondary metabolism could produce more than one product owing to the substrate tolerance of the introduced enzyme.

Third, the introduction of a gene into an organism could disturb secondary metabolite production simply as a consequence of the random gene insertion, with unplanned and unexpected increases in the content of some compounds, owing to changes in the metabolic flux through matrix pathways.

In the Briefing1 it was suggested that metabolite profiling or clinical trials might help address the issue of the unknown consequences of manipulating food composition. Both these approaches might be very helpful when assessing the consequences of introducing a single major product, but they would be less productive when assessing the consequences of interfering with secondary metabolism.

Of major concern is the fact that the secondary metabolite profiles of plants can vary considerably, so the effect of introducing a gene into a plant might be predictable only under defined conditions that may not be achievable in the field. The secondary metabolite profile is complex, and extremely small amounts of highly potent compounds can have profound biological consequences — how complete would metabolite profiling have to be?


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Firn, R., Jones, C. Secondary metabolism and the risks of GMOs. Nature 400, 13–14 (1999).

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