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.

我们之前通过大肠杆菌的高通量实验室进化发现，一种l-谷氨酰胺类似物l-谷氨酸 γ-酰肼具有高诱变活性。本研究通过Ames试验和大肠杆菌突变积累实验检测了L-谷氨酸γ-酰肼的致突变性和突变特性。Ames 试验表明，与已知的诱变剂 2-氨基蒽和醋酸钴 (II) 四水合物相比，L-谷氨酸 γ-酰肼在没有代谢激活的情况下表现出更高的诱变活性。该结果表明L-谷氨酸 γ-酰肼在大肠杆菌。突变积累实验和全基因组测序分析揭示了有或没有l-谷氨酸γ-酰肼的积累突变的数量和谱。在l-谷氨酸 γ-酰肼存在下，MDS42 菌株在 30 代累积了 392.3 ± 116.2 点突变，对应于 777 代，而 MDS42 菌株在没有l-谷氨酸 γ-酰肼的 50 代期间累积了 1.5 ± 2.5 点突变，对应于1341代。L-谷氨酸γ-酰肼的突变谱为G/C向A/T转变（82.2±4.3%）和A/T向G/C转变（17.4±4.3%）。这些结果表明，l-谷氨酸γ-酰肼具有很强的诱变活性。