Characterization and safety evaluation of HPPD W336, a modified 4-hydroxyphenylpyruvate dioxygenase protein, and the impact of its expression on plant metabolism in herbicide-tolerant MST-FGØ72-2 soybean

• Published in: Regulatory toxicology and pharmacology Vol. 97; pp. 170 - 185
• Main Authors: Dreesen, Rozemarijn, Capt, Annabelle, Oberdoerfer, Regina, Coats, Isabelle, Pallett, Kenneth, Edward
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.08.2018
• Subjects: 4-Hydroxyphenylpyruvate dioxygenase; 4-Hydroxyphenylpyruvate Dioxygenase - metabolism; Allergenicity assessment; Amino Acid Sequence; Amino Acids, Aromatic - chemistry; Amino Acids, Aromatic - metabolism; Characterization; Functional and structural equivalence; Genetically modified crop; Glycine max - drug effects; Glycine max - genetics; Glycine max - metabolism; Herbicides - toxicity; HPPD W336; MST-FGØ72-2 soybean; Overexpression; Phenotype; Plants, Genetically Modified - metabolism; Pseudomonas fluorescens - enzymology; Safety assessment; Tyrosine - metabolism; 4-Hydroxyphenylpyruvate dioxygenase; Characterization; Overexpression; Safety assessment; Allergenicity assessment; HPPD W336; Functional and structural equivalence; Genetically modified crop; MST-FGØ72-2 soybean
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2018.06.002

By transgenic expression technology, a modified 4-hydroxyphenylpyruvate dioxygenase enzyme (HPPD W336) originating from Pseudomonas fluorescens is expressed in MST-FGØ72-2 soybean to confer tolerance to 4-benzoyl isoxazole and triketone type of herbicides. Characterization and safety assessment of HPPD W336 were performed. No relevant sequence homologies were found with known allergens or toxins. Although sequence identity to known toxins showed identity to HPPD proteins annotated as hemolysins, the absence of hemolytic activity of HPPD W336 was demonstrated in vitro. HPPD W336 degrades rapidly in simulated gastric fluid. The absence of toxicity and hemolytic potential of HPPD W336 was confirmed by in vivo studies. The substrate spectrum of HPPD W336 was compared with wild type HPPD proteins, demonstrating that its expression is unlikely to induce any metabolic shifts in soybean. The potential effect of expression of HPPD W336 on metabolic pathways related to tyrosine was investigated by comparing seed composition of MST-FGØ72-2 soybean with non-genetically modified varieties, demonstrating that expression of HPPD W336 does not change aromatic amino acid, homogentisate and tocochromanol levels. In conclusion, HPPD W336 was demonstrated to be as safe as other food proteins. No adverse metabolic effects were identified related to HPPD W336 expression in MST-FGØ72-2 soybean. [Display omitted] •Safety assessment shows no evidence for toxicity or allergenicity of HPPD W336.•The modification in HPPD W336 has negligible impact on substrate specificity.•No metabolic shift was identified upon HPPD W336 expression in MST-FGØ72-2 soybean.