标题：Construction ofEscherichia coliWhole-Cell Biosensors for Statin Efficacy and Production Test
作者：Li, Huanjie; Wang, Qingda; Zhao, Rui; Wang, Yunshan; Xun, Luying; Liu, Huaiwei
作者机构：[Li, Huanjie; Wang, Yunshan] Shandong Univ, Sch Med, Cheeloo Coll Med, Jinan, Peoples R China.; [Li, Huanjie; Wang, Qingda; Zhao, Rui; Xun, Luying; 更多
通讯作者地址：Liu, HW (corresponding author), Shandong Univ, State Key Lab Microbial Technol, Qingdao, Peoples R China.
来源：FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
关键词：synthetic biology; biosensor; statin; precision medicine; HMGR
摘要：Statins are widely used cholesterol-lowering drugs. Their potential application in anti-cancer treatment is also under investigation. The individual variance in statin response has been observed, which may be caused by the variation in human HMG-CoA reductase (hHMGR)-the inhibition target of statin drugs. Herein, we reported the design and construction of twoEscherichia coliwhole-cell biosensors. The first one is statin-efficacy testing sensor, which is composed of two separate modules: a hybrid mevalonate (MVA) pathway and a HMG-CoA sensing system. A truncated hHMGR was used as the key enzyme of the MVA pathway and a promiscuous transcription factor (TF) BsFapR was used as the HMG-CoA sensor. When hHMGR was inhibited by statins, HMG-CoA accumulated intracellularly and was sensed by BsFapR, which subsequently turned on its cognate promoter. This biosensor has the potential to be used as a "precision medicine" tool-selecting potent statin drugs for individual patients. The second one is a statin-production testing sensor, which is based on another promiscuous TF AraCM that can sense statins. This biosensor can be used in optimization of statin-producing strains. The prototypes of these two biosensors were successfully constructed and their further optimization is highly expected.