title: A gene-shuffled glyphosate acetyltransferase protein from Bacillus licheniformis (GAT4601) shows no evidence of allergenicity or toxicity.
abstract: The glyphosate acetyltransferase (gat) gene from Bacillus licheniformis was subjected to multiple rounds of gene shuffling to optimize kinetics of corresponding GAT proteins to acetylate the herbicide active ingredient glyphosate. Genetically modified soybeans expressing the gat4601 gene (356043 soybeans) are tolerant to the application of glyphosate. The current manuscript reports the outcome of the allergenicity and toxicity assessment for the GAT4601 protein. Bioinformatic comparison of the amino acid sequence of GAT4601 did not identify similarities to known allergenic or toxic proteins. In vitro studies conducted with heterologously produced GAT4601 protein demonstrated that it was rapidly degraded in simulated gastric fluid containing pepsin (< 30 s) and in simulated intestinal fluid containing pancreatin (< 2 min) and completely inactivated at temperatures above 56 degrees C. The GAT4601 protein expressed in planta is not glycosylated and similar protein profiles were observed in flour extracts from 356043 soybeans and nontransgenic near isoline comparator soybeans (Jack) using serum from soy allergic persons. No evidence of adverse effects was observed in mice following acute oral exposure to 2000 mg/kg of GAT4601 protein or in a repeated dose dietary exposure study at doses of 800-1000 mg/kg/day. This comprehensive assessment demonstrates that the GAT4601 protein does not present a risk for adverse effects in humans when used in the context of agricultural biotechnology.
authors: Pioneer Hi-Bred International, Inc., Johnston, Iowa 50131, USA.
authors: Bryan
authors: B
authors: Delaney
authors: John
authors: J
authors: Zhang
authors: Gabrielle
authors: G
authors: Carlson
authors: Jean
authors: J
authors: Schmidt
authors: Barb
authors: B
authors: Stagg
authors: Brad
authors: B
authors: Comstock
authors: Amy
authors: A
authors: Babb
authors: Carol
authors: C
authors: Finlay
authors: Robert F
authors: RF
authors: Cressman
authors: Greg
authors: G
authors: Ladics
authors: Amarin
authors: A
authors: Cogburn
authors: Dan
authors: D
authors: Siehl
authors: Luda
authors: L
authors: Bardina
authors: Hugh
authors: H
authors: Sampson
authors: Youngshin
authors: Y
authors: Han
mesh_terms: D000123:Acetyltransferases / Q000737:chemistry / Q000276:immunology / Q000633:toxicity*; D000485:Allergens / Q000737:chemistry / Q000276:immunology / Q000633:toxicity*; D000595:Amino Acid Sequence; D000821:Animal Feed; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001407:Bacillus / Q000201:enzymology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology / Q000633:toxicity*; D005512:Food Hypersensitivity / Q000276:immunology*; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D030821:Plants, Genetically Modified; D015202:Protein Engineering / Q000379:methods; D013025:Glycine max / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D018675:Toxicity Tests
chemical_list: D000485:Allergens; D001426:Bacterial Proteins; D000123:Acetyltransferases; C486861:glyphosate N-acetyltransferase