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 e 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.
Keywords: biosensor; genetic promoter chip; high-throughput screening (HTS); promoter; sensitivity; specificity; toxicity; “push and pull” mode.