Mutational property of newly identified mutagen l-glutamic acid γ-hydrazide in Escherichia coli.

Autor: Maeda T; RIKEN Center for Biosystems Dynamics Research, 6-2-3 Furuedai, Suita, Osaka, 565-0874, Japan. Electronic address: tomoya.maeda@chem.agr.hokudai.ac.jp., Shibai A; RIKEN Center for Biosystems Dynamics Research, 6-2-3 Furuedai, Suita, Osaka, 565-0874, Japan., Yokoi N; RIKEN Center for Biosystems Dynamics Research, 6-2-3 Furuedai, Suita, Osaka, 565-0874, Japan., Tarusawa Y; RIKEN Center for Biosystems Dynamics Research, 6-2-3 Furuedai, Suita, Osaka, 565-0874, Japan., Kawada M; RIKEN Center for Biosystems Dynamics Research, 6-2-3 Furuedai, Suita, Osaka, 565-0874, Japan., Kotani H; RIKEN Center for Biosystems Dynamics Research, 6-2-3 Furuedai, Suita, Osaka, 565-0874, Japan., Furusawa C; RIKEN Center for Biosystems Dynamics Research, 6-2-3 Furuedai, Suita, Osaka, 565-0874, Japan; Department of Physics, The University of Tokyo, 7-3-1 Hongo, Tokyo, 113-0033, Japan; Universal Biology Institute, The University of Tokyo, 7-3-1 Hongo, Tokyo, 113-0033, Japan.
Jazyk: angličtina
Zdroj: Mutation research [Mutat Res] 2021 Jul-Dec; Vol. 823, pp. 111759. Date of Electronic Publication: 2021 Jul 21.
DOI: 10.1016/j.mrfmmm.2021.111759
Abstrakt: We previously found that an l-glutamine analog l-glutamic acid γ-hydrazide has high mutagenic activity through the high-throughput laboratory evolution of Escherichia coli. In this study, mutagenicity and mutational property of l-glutamic acid γ-hydrazide were examined by the Ames test and mutation accumulation experiments using E. coli. The Ames test revealed that l-glutamic acid γ-hydrazide showed higher mutagenic activity without metabolic activation than known mutagens 2-aminoanthracene, and cobalt(II) acetate tetrahydrate. This result indicates that l-glutamic acid γ-hydrazide does not require metabolic activation for mutagenic activity in E. coli. Mutation accumulation experiments and whole-genome sequencing analysis revealed the number and spectrum of the accumulated mutations with or without l-glutamic acid γ-hydrazide. In the presence of l-glutamic acid γ-hydrazide, MDS42 strain accumulated 392.3 ± 116.2 point mutations during 30 passages corresponding to 777 generations, while MDS42 strain accumulated 1.5 ± 2.5 point mutations without l-glutamic acid γ-hydrazide during 50 passages corresponding to 1341 generations. The mutational spectrum of l-glutamic acid γ-hydrazide was G/C to A/T transition (82.2 ± 4.3 %) and A/T to G/C transition (17.4 ± 4.3 %). These results indicated that l-glutamic acid γ-hydrazide has a strong mutagenic activity.
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Databáze: MEDLINE