Cyanobacteria are oxygen-evolving photosynthetic autotrophs essential for nutrient cycling in the environment. They possess multiple control mechanisms for their cellular activities in order to adapt to the environment. While protein translation is essential for cell survival and adaptation, the regulation and the flexibility of this process are poorly understood in cyanobacteria. β-N-methylamino-L-alanine (BMAA), an amino acid analog proposed as an environmental neurotoxin, is highly toxic to the filamentous diazotrophic cyanobacterium Anabaena PCC 7120. In this study, through genetic analysis of BMAA-resistant mutants, we demonstrate that the system responsible for modification of ANN-decoding tRNAs with N(6)-threonylcarbamoyl adenosine (t⁶A) is involved in BMAA sensitivity through the control of translation. Both BMAA and inactivation of the t⁶A biosynthesis pathway affect translational fidelity and ribosome assembly. However, the two factors display either additive effects on translational elongation, or attenuate each other over translational fidelity or the resistance/sensitivity to antibiotics that inhibit different steps of the translational process. BMAA has a broad effect on translation and transcription, and once BMAA enters the cells, the presence of the t⁶A biosynthesis pathway increases the sensitivity of the cells towards this toxin. BMAA-resistant mutants screening is an effective method for getting insight into the toxic mechanisms of BMAA. In addition, BMAA is a useful tool for probing translational flexibility of cyanobacteria, and the characterization of the corresponding resistant mutants should help us to reveal translational mechanism allowing cyanobacteria to adapt to changing environments.

蓝藻是环境中养分循环所必需的产氧光合自养生物。它们具有多种细胞活动控制机制，以适应环境。虽然蛋白质翻译对于细胞存活和适应至关重要，但在蓝藻中对该过程的调节和灵活性知之甚少。β-N-甲基氨基-L-丙氨酸 (BMAA) 是一种氨基酸类似物，被认为是一种环境神经毒素，对丝状固氮蓝藻Anabaena PCC 7120 具有剧毒。在本研究中，通过对 BMAA 抗性突变体的遗传分析，我们证明了负责用 N(6)-苏氨酰氨基甲酰腺苷修饰 ANN 解码 tRNA 的系统（t ⁶A) 通过翻译控制参与 BMAA 敏感性。BMAA 和t ⁶ A 生物合成途径的失活都会影响翻译保真度和核糖体组装。然而，这两个因素要么对平移延伸显示出累加效应，要么在平移保真度或对抑制平移过程不同步骤的抗生素的抗性/敏感性上相互减弱。BMAA 对翻译和转录有广泛的影响，一旦 BMAA 进入细胞，t ⁶生物合成途径增加了细胞对这种毒素的敏感性。BMAA抗性突变体筛选是深入了解BMAA毒性机制的有效方法。此外，BMAA 是探索蓝藻翻译灵活性的有用工具，相应的抗性突变体的表征应该有助于我们揭示使蓝藻适应不断变化的环境的翻译机制。