Abstract

A promoter is a small region of a DNA sequence that responds to various transcription factors, which initiates a particular gene expression. The promoter-engineered biosensor can activate or repress gene expression through a transcription factor recognizing specific molecules, such as polyamine, sugars, lactams, amino acids, organic acids, or a redox molecule; however, there are few reported applications of promoter-enhanced biosensors. This review paper highlights the strategies of construction of promoter gene-engineered biosensors with human and bacteria genetic promoter arrays with regard to high-throughput screening (HTS) molecular drugs, the study of the membrane protein’s localization and nucleocytoplasmic shuttling mechanism of regulating factors, enzyme activity, detection of the toxicity of intermediate chemicals, and probing bacteria density to improve value-added product titer. These biosensors’ sensitivity and specificity can be further improved by the proposed approaches of Mn2+ and Mg2+ added random error-prone PCR that is a technique used to generate randomized genomic libraries and site-directed mutagenesis approach, which is applied for the construction of bacteria’s “mutant library”. This is expected to establish a flexible HTS platform (biosensor array) to large-scale screen transcription factor-acting drugs, reduce the toxicity of intermediate compounds, and construct a gene-dynamic regulatory system in “push and pull” mode, in order to effectively regulate the valuable medicinal product production. These proposed novel promoter-engineered biosensors aiding in synthetic genetic circuit construction will maximize the efficiency of the bio-synthesis of medicinal compounds, which will greatly promote the development of microbial metabolic engineering and biomedical science.

Highlights

  • With the development of life sciences and DNA molecular technology, we can discover the key gene, new enzyme, or protein that controls the main signaling pathway for synthesis of a desired product

  • Many genes or enzymes are directly regulated by a transcription factor without effector binding; some genes need a transcription factor, and compound effector binding for dynamically controlling gene expression [1,2]

  • We found that in the membrane protein of E. coli, YojI can mediate the interaction of E. coli and human brain microvascular endothelial cells (HBMECs), by using both the human and E. coli proteome chips in conjunction with cell labeling techniques for the discovery of microbial and host factors

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Summary

Introduction

With the development of life sciences and DNA molecular technology, we can discover the key gene, new enzyme, or protein that controls the main signaling pathway for synthesis of a desired product. Many genes or enzymes are directly regulated by a transcription factor without effector binding; some genes need a transcription factor, and compound effector binding for dynamically controlling gene expression [1,2]. Access to large of quantities of these dynamic regulatory components is critical for the discovery of new biosensors for novel applications [3,4,5]. Promoters, transcription factors and molecular effectors collectively contribute to the discovery of biosensors and significantly draw our attention (Table 1). Promoters, transcription factors and molecular effectors collectively contribute to and significantly draw our attention (Table 1)

Strategies for the Construction of Promoter-Enhanced Biosensor
Synthesizing Promoters to Increase Their Properties
Approaches
Construction
Discussion and Conclusions
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