Construction of Escherichia coli Whole-Cell Biosensors for Statin Efficacy and Production Test

Huanjie Li; Qingda Wang; Rui Zhao; Yunshan Wang; Luying Xun; Huaiwei Liu

doi:10.3389/fcell.2020.00404

Construction of Escherichia coli Whole-Cell Biosensors for Statin Efficacy and Production Test

Front Cell Dev Biol. 2020 May 28:8:404. doi: 10.3389/fcell.2020.00404. eCollection 2020.

Authors

Huanjie Li^{1

2

3}, Qingda Wang², Rui Zhao², Yunshan Wang^{1

3}, Luying Xun^{2

4}, Huaiwei Liu²

Affiliations

¹ School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.
² State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China.
³ Medical Research and Laboratory Diagnostic Center, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
⁴ School of Molecular Biosciences, Washington State University, Pullman, WA, United States.

Abstract

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 two Escherichia coli whole-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.

Keywords: HMGR; biosensor; precision medicine; statin; synthetic biology.