A gene-shuffled glyphosate acetyltransferase protein from Bacillus licheniformis (GAT4601) shows no evidence of allergenicity or toxicity.
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.
Delaney
Bryan
B
Pioneer Hi-Bred International, Inc., Johnston, Iowa 50131, USA.
Zhang
John
J
Carlson
Gabrielle
G
Schmidt
Jean
J
Stagg
Barb
B
Comstock
Brad
B
Babb
Amy
A
Finlay
Carol
C
Cressman
Robert F
RF
Ladics
Greg
G
Cogburn
Amarin
A
Siehl
Dan
D
Bardina
Luda
L
Sampson
Hugh
H
Han
Youngshin
Y
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
D000485:Allergens; D001426:Bacterial Proteins; D000123:Acetyltransferases; C486861:glyphosate N-acetyltransferase