Department of BioSciences, Rice University, Houston, TX, USA.
Department of BioSciences, Rice University, Houston, TX, USA; Department of Bioengineering, Rice University, Houston, TX, USA; Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, USA.
Biosens Bioelectron. 2024 Jan 1;243:115762. doi: 10.1016/j.bios.2023.115762. Epub 2023 Oct 17.
Redox-active small molecules containing quinone functional groups play important roles as pharmaceuticals, but can be toxic if overdosed. Despite the need for a fast and quantitative method to detect quinone and its derivatives, current sensing strategies are often slow and struggle to differentiate between structural analogs. Leveraging the discovery that microorganisms use certain quinones to perform extracellular electron transfer (EET), we investigated the use of Lactiplantibacillus plantarum as a whole-cell bioelectronic sensor to selectively sense quinone analogs. By tailoring the native EET pathway in L. plantarum, we enabled quantitative quinone sensing of 1,4-dihydroxy-2-naphthoic acid (DHNA) - a gut bifidogenic growth stimulator. We found that L. plantarum could respond to environmental DHNA within seconds, producing concentration-dependent electrical signals. This sensing capacity was robust in different assay media and allowed for continuous monitoring of DHNA concentrations. In a simulated gut environment containing a mixed pool of quinone derivatives, this tailored EET pathway can selectively sense pharmacologically relevant quinone analogs, such as DHNA and menadione, amongst other structurally similar quinone derivatives. We also developed a multivariate model to describe the mechanism behind this selectivity and found a predictable correlation between quinone physiochemical properties and the corresponding electrical signals. Our work presents a new concept to selectively sense quinone using whole-cell bioelectronic sensors and opens the possibility of using probiotic L. plantarum for bioelectronic applications in human health.
含醌官能团的氧化还原活性小分子在药物治疗中发挥着重要作用，但如果过量使用可能会有毒性。尽管需要一种快速且定量的方法来检测醌及其衍生物，但当前的传感策略往往速度较慢，难以区分结构类似物。利用微生物利用某些醌进行细胞外电子转移（EET）的发现，我们研究了利用植物乳杆菌作为全细胞生物电子传感器来选择性地感应醌类似物。通过调整植物乳杆菌中原生的 EET 途径，我们实现了对 1,4-二羟基-2-萘甲酸（DHNA）的定量醌感应 - 一种肠道双歧杆菌生长刺激剂。我们发现，植物乳杆菌可以在几秒钟内对环境中的 DHNA 做出反应，产生浓度依赖性的电信号。这种传感能力在不同的测定介质中都很稳健，并允许对 DHNA 浓度进行连续监测。在含有混合醌衍生物池的模拟肠道环境中，这种定制的 EET 途径可以选择性地感应出具有药理相关性的醌类似物，如 DHNA 和维生素 K3，以及其他结构相似的醌衍生物。我们还开发了一个多元模型来描述这种选择性背后的机制，并发现了醌物理化学性质与相应电信号之间可预测的相关性。我们的工作提出了使用全细胞生物电子传感器选择性感应醌的新概念，并为利用益生菌植物乳杆菌在人类健康中的生物电子应用开辟了可能性。
