Transcription factor-based biosensors naturally occur in metabolic pathways to maintain cell growth and to provide a robust response to environmental fluctuations. Extended metabolic biosensors, i.e., the cascading of a bio-conversion pathway and a transcription factor (TF) responsive to the downstream effector metabolite, provide sensing capabilities beyond natural effectors for implementing context-aware synthetic genetic circuits and bio-observers. However, the engineering of such multi-step circuits is challenged by stability and robustness issues. In order to streamline the design of TF-based biosensors in metabolic pathways, here we investigate the response of a genetic circuit combining a TF-based extended metabolic biosensor with an antithetic integral circuit, a feedback controller that achieves robustness against environmental fluctuations. The dynamic response of an extended biosensor-based regulated flavonoid pathway is analyzed in order to address the issues of biosensor tuning of the regulated pathway under industrial biomanufacturing operating constraints.

基于转录因子的生物传感器天然存在于代谢途径中，以维持细胞生长并提供对环境波动的强大响应。扩展的代谢生物传感器，即级联生物转化途径和对下游效应子代谢产物有反应的转录因子（TF），可提供超出自然效应器的感知能力，以实现情境感知的合成遗传电路和生物观察者。然而，这种多步电路的工程设计受到稳定性和鲁棒性问题的挑战。为了简化新陈代谢途径中基于TF的生物传感器的设计，在这里我们研究了结合基于TF的扩展代谢生物传感器和对立积分电路的遗传电路的响应，一个能够抵抗环境波动的鲁棒性的反馈控制器。分析了扩展的基于生物传感器的调节类黄酮途径的动态响应，以解决在工业生物制造操作限制下调节途径的生物传感器调节的问题。