Transcription factor-based biosensors for screening and dynamic regulation

Abstract

Advances in synthetic biology and genetic engineering are bringing into the spotlight a wide range of bio-based applications that demand better sensing and control of biological behaviours. Transcription factor (TF)-based biosensors are promising tools that can be used to detect several types of chemical compounds and elicit a response according to the desired application. However, the wider use of this type of device is still hindered by several challenges, which can be addressed by increasing the current metabolite-activated transcription factor knowledge base, developing better methods to identify new transcription factors, and improving the overall workflow for the design of novel biosensor circuits. These improvements are particularly important in the bioproduction field, where researchers need better biosensor-based approaches for screening production-strains and precise dynamic regulation strategies. In this work, we summarize what is currently known about transcription factor-based biosensors, discuss recent experimental and computational approaches targeted at their modification and improvement, and suggest possible future research directions based on two applications: bioproduction screening and dynamic regulation of genetic circuits.

Biological Responses of Pacific Herring Embryos to Crude Oil Are Quantifiable at Exposure Levels Below Conventional Limits of Quantitation for PAHs in Water and Tissues

“…Looking forward, it may be possible to develop novel, highly sensitive methods for quantifying PAHs using the PAH-inducible DNA binding/ transcriptional activation function of the AHR as a biosensor. 43 We and others have quantified a wide range of cardiotoxicity end points in oil-exposed embryos across a diversity of fish species. These metrics include edema accumulation (a measure of cardiac output), heart rate, heart rhythm, chamber contractility (measured as fractional shortening), chamber area-based volumetric cardiac output (a derivative of fractional shortening), chamber looping (atrioventricular angle), total chamber area for the atrium and ventricle, and area of the posterior ventricle (ballooning).…”

“…On the other hand, the sensitivity of fish embryos as integrators of exposure demonstrated here in the laboratory and in the field, , for both exposure and effect biomarkers, reinforces the advantages of biomonitoring over chemical measurements in environmental assessments of petroleum pollution impacts. Looking forward, it may be possible to develop novel, highly sensitive methods for quantifying PAHs using the PAH-inducible DNA binding/transcriptional activation function of the AHR as a biosensor …”

Synthetic cell-based biosensors and methods for discovering novel sensing elements

“…In cell-free assays, transcription and translation machinery extracted from cells is reserved, but substances for cell growth, movement, metabolism or other activity are removed. When applied in the construction of synthetic biosensors, cell-free assay simplifies the expression of genetic circuits and expedites the selection of qualified sensing elements [5]. Moreover, if the working mechanism of the biosensor precludes the expression of proteins, it can function straightforward in cell-free conditions.…”

Applications and Tuning Strategies for Transcription Factor-Based Metabolite Biosensors

“…The latter half of this review is dedicated to three important applications of metabolite biosensors: high-throughput screening, visualizing metabolite dynamics and performing dynamic metabolic regulation, and investigating metabolic heterogeneity. High-throughput screening and dynamic regulation are well-established applications of TF-based biosensors with key roles in biosensor discovery and metabolic control [ 15 , 34 ]. We will further highlight the use of TF-based sensors for the study and control of metabolic heterogeneity, which has critical implications in our understanding of single-cell behavior and large-scale bioproduction.…”