Bacteria equipped with genetically-encoded lactate biosensors would support several applications in biopharmaceutical production, diagnosis, or therapeutics. However, many applications involve glucose-rich and anaerobic environments, in which current whole-cell lactate biosensors have low performance. Here we engineered a synthetic lactate biosensor system by repurposing the natural LldPRD promoter regulated by the LldR transcriptional regulator. We removed glucose catabolite repression by designing a hybrid promoter, containing LldR operators and tuned both regulator and reporter gene expression to optimize biosensor signal-to-noise ratio. The resulting lactate biosensor, termed ALPaGA (A Lactate Promoter Operating in Glucose and Anaerobia) can operate in glucose rich, aerobic and anaerobic conditions. Our work provides a versatile lactate biosensing platform suitable for many environmental conditions.

中文翻译：

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在富葡萄糖和厌氧环境中运行的工程化的乳酸响应启动子系统。

配备有基因编码的乳酸生物传感器的细菌将支持生物制药生产，诊断或治疗中的多种应用。然而，许多应用涉及富含葡萄糖和厌氧的环境，在这种环境中，当前的全细胞乳酸生物传感器性能低下。在这里，我们通过重新利用由LldR转录调节因子调节的天然LldPRD启动子，设计了一个合成的乳酸生物传感器系统。我们通过设计包含LldR操纵子的杂合启动子消除了葡萄糖分解代谢物的阻遏作用，并调节了调节子和报告基因的表达，以优化生物传感器的信噪比。所得的乳酸生物传感器称为ALPaGA（在葡萄糖和厌氧菌中运行的乳酸促进剂）可以在葡萄糖含量高，需氧和厌氧的条件下运行。