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


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.

SUBMITTER: Li H 

PROVIDER: S-EPMC7326143 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Construction of <i>Escherichia coli</i> Whole-Cell Biosensors for Statin Efficacy and Production Test.

Li Huanjie H   Wang Qingda Q   Zhao Rui R   Wang Yunshan Y   Xun Luying L   Liu Huaiwei H  

Frontiers in cell and developmental biology 20200528


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 <i>Escherichia coli</i> whole-cell biosensors. The first one is statin-efficacy testing sensor, which is composed of two separate modules:  ...[more]

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