Safety of the Bacillus thuringiensis-derived Cry1A.105 protein: Evidence that domain exchange preserves mode of action and safety.

Autor: Wang C; Bayer U.S., Crop Science Division, 700 Chesterfield Pkwy West, Chesterfield, MO 63017, USA. Electronic address: Cunxi.wang@bayer.com., Li W; Bayer U.S., Crop Science Division, 700 Chesterfield Pkwy West, Chesterfield, MO 63017, USA., Kessenich CR; Bayer U.S., Crop Science Division, 700 Chesterfield Pkwy West, Chesterfield, MO 63017, USA., Petrick JS; Bayer U.S., Crop Science Division, 700 Chesterfield Pkwy West, Chesterfield, MO 63017, USA., Rydel TJ; Bayer U.S., Crop Science Division, 700 Chesterfield Pkwy West, Chesterfield, MO 63017, USA., Sturman EJ; Bayer U.S., Crop Science Division, 700 Chesterfield Pkwy West, Chesterfield, MO 63017, USA., Lee TC; Bayer U.S., Crop Science Division, 700 Chesterfield Pkwy West, Chesterfield, MO 63017, USA., Glenn KC; Bayer U.S., Crop Science Division, 700 Chesterfield Pkwy West, Chesterfield, MO 63017, USA., Edrington TC; Bayer U.S., Crop Science Division, 700 Chesterfield Pkwy West, Chesterfield, MO 63017, USA. Electronic address: thomas.edrington@bayer.com.
Jazyk: angličtina
Zdroj: Regulatory toxicology and pharmacology : RTP [Regul Toxicol Pharmacol] 2018 Nov; Vol. 99, pp. 50-60. Date of Electronic Publication: 2018 Sep 06.
DOI: 10.1016/j.yrtph.2018.09.003
Abstrakt: The lepidopteran-active Cry1A.105 protein is a chimeric three-domain insecticidal toxin with distinct structural domains derived from the naturally occurring Cry1Ab, Cry1Ac and Cry1F proteins from the soil bacterium Bacillus thuringiensis (Bt). The X-ray crystal structure of the Cry1A.105 tryptic core at 3.0 Å resolution demonstrates its high structural similarity to the tryptic core of Cry1Ac. Bioinformatics analyses demonstrate that Cry1A.105 has no significant amino acid sequence similarity to known allergens or mammalian toxins, which is the same conclusion reached for its component domains. Like its intact donor proteins, Cry1A.105 was heat labile at temperatures ≥75 °C and degraded upon exposure to gastrointestinal proteases. No adverse effects were observed in mice when Cry1A.105 was dosed orally at 2451 mg/kg body weight. Therefore, the weight of evidence supports that Cry1A.105 is safe for human and animal consumption. These results support the conclusion that the safety of a chimeric protein for human or animal consumption can be evaluated in the context of the safety of its donor proteins.
(Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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