Protein familiarity is a fundamental but rarely operationalized concept in the safety assessment of genetically modified crops: example of phosphomannose isomerase (PMI).

Fundamental to the safety assessment of genetically modified (GM) crops is the concept of negligible risk for newly expressed proteins for which there is a history of safe use. Although this simple concept has been stated in international and regional guidance for assessing the risk of newly expressed proteins in GM crops, its full implementation by regulatory authorities has been lacking. As a result, safety studies are often repeated at a significant expenditure of resources by developers, study results are repeatedly reviewed by regulators, and animals are sacrificed needlessly to complete redundant animal toxicity studies. This situation is illustrated using the example of the selectable marker phosphomannose isomerase (PMI) for which familiarity has been established. Reviewed is the history of safe use for PMI and predictable results of newly conducted safety studies including bioinformatic comparisons, resistance to digestion, and acute toxicity that were repeated to gain regulatory reapproval of PMI expressed from constructs in recently developed GM maize. As expected, the results of these newly repeated hazard-identification and characterization studies for PMI indicate negligible risk. PMI expressed in recently developed GM crops provides an opportunity to use the concept of familiarity by regulatory authorities to reduce risk-disproportionate regulation of these new events and lessen the resulting waste of both developer and regulator resources, as well as eliminate unnecessary animal testing. This would also correctly imply that familiar proteins like PMI have negligible risk. Together, such modernization of regulations would benefit society through enabling broader and faster access to needed technologies.

Safety assessment of the insecticidal protein IPD079Ea from the fern, Ophioglossum pendulum.

As agricultural biotechnology continues to develop solutions for addressing crop pests through newly expressed proteins from novel source organisms, with different modes or sites of action and/or different spectra of activity, the safety of these proteins will be assessed. The results of hazard-identification and characterization studies for the insecticidal protein IPD079Ea, which is derived from a fern (Ophioglossum pendulum) and active against the maize pest western corn rootworm (Diabrotica virgifera virgifera, Coleoptera: Chrysomelidae) are provided. Collectively these results indicate that IPD079Ea is unlikely to present a hazard to human or animal health and support the safety of genetically modified maize expressing IPD079Ea.

N-acetylglutamate and N-acetylaspartate in soybeans (Glycine max L.), maize (Zea mays L.), [corrected] and other foodstuffs.

N-Acetylglutamate (NAG) and N-acetylaspartate (NAA) are amino acid derivatives with reported activities in a number of biological processes. However, there is no published information on the presence of either substance in foodstuffs. We developed a method for extracting and quantifying NAG and NAA from soybean seeds and maize grain using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). The lower limit of quantification for both NAG and NAA was 1 ng/mL. The method was then utilized to quantify NAG and NAA in other foodstuffs (fruits, vegetables, meats, grains, milk, coffee, tea, cocoa, and others). Both NAG and NAA were present in all of the materials analyzed. The highest concentration of NAG was found in cocoa powder. The highest concentration of NAA was found in roasted coffee beans. Both NAG and NAA were found at quantifiable concentrations in all foods tested indicating that these two acetylated amino acids are common components of the human diet.

Metabolic engineering to increase isoflavone biosynthesis in soybean seed.

Isoflavone levels in Glycine max (soybean) were increased via metabolic engineering of the complex phenylpropanoid biosynthetic pathway. Phenylpropanoid pathway genes were activated by expression of the maize C1 and R transcription factors in soybean seed, which decreased genistein and increased the daidzein levels with a small overall increase in total isoflavone levels. Cosuppression of flavanone 3-hydroxylase to block the anthocyanin branch of the pathway, in conjunction with C1/R expression, resulted in higher levels of isoflavones. The combination of transcription factor-driven gene activation and suppression of a competing pathway provided a successful means of enhancing accumulation of isoflavones in soybean seed.