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Genetically Encoded, Small-Molecule Biosensors and Their Applications

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A special issue of Biosensors (ISSN 2079-6374). This special issue belongs to the section "Biosensors and Healthcare".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 8407

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Special Issue Editor

Dr. Patrick C. Cirino

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Guest Editor

Department of Chemical and Biomolecular Engineering, University of Houston, Houston, TX 77204-4004, USA
Interests: biocatalysis; protein engineering; metabolic engineering; directed evolution; high-throughput screening; biosensors

Special Issue Information

Dear Colleagues,

Genetically encoded biosensors are proteins or nucleic acids that, when actuated by specific signals, elicit readily detectable cellular change(s) or trigger other, targeted genetic and metabolic responses to those signals. This Special Issue will feature new research into the design or repurposing of endogenously expressed biosensors that target specific small molecules, along with their applications. Example applications include coupling biosensing to outputs amenable to high-throughput screening of single cells, and use as novel dynamic regulators of uni- or multi-cellular processes.

Dr. Patrick C. Cirino
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biosensors is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

biosensing
synthetic biology
directed evolution
metabolic engineering
computational design
transcription factor
aptamer

Published Papers (4 papers)

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Research

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14 pages, 1143 KiB

Open AccessArticle

MoBioS: Modular Platform Technology for High-Throughput Construction and Characterization of Tunable Transcriptional Biological Sensors

by Wouter Demeester, Jasmine De Baets, Dries Duchi, Marjan De Mey and Brecht De Paepe

Biosensors 2023, 13(6), 590; https://doi.org/10.3390/bios13060590 - 30 May 2023

Cited by 1 | Viewed by 1954

Abstract

All living organisms have evolved and fine-tuned specialized mechanisms to precisely monitor a vast array of different types of molecules. These natural mechanisms can be sourced by researchers to build Biological Sensors (BioS) by combining them with an easily measurable output, such as fluorescence. Because they are genetically encoded, BioS are cheap, fast, sustainable, portable, self-generating and highly sensitive and specific. Therefore, BioS hold the potential to become key enabling tools that stimulate innovation and scientific exploration in various disciplines. However, the main bottleneck in unlocking the full potential of BioS is the fact that there is no standardized, efficient and tunable platform available for the high-throughput construction and characterization of biosensors. Therefore, a modular, Golden Gate-based construction platform, called MoBioS, is introduced in this article. It allows for the fast and easy creation of transcription factor-based biosensor plasmids. As a proof of concept, its potential is demonstrated by creating eight different, functional and standardized biosensors that detect eight diverse molecules of industrial interest. In addition, the platform contains novel built-in features to facilitate fast and efficient biosensor engineering and response curve tuning. Full article

(This article belongs to the Special Issue Genetically Encoded, Small-Molecule Biosensors and Their Applications)

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8 pages, 3550 KiB

Open AccessCommunication

Insight into the Mode of Action of 8-Hydroxyquinoline-Based Blockers on the Histamine Receptor 2

by Amisha Patel, Paola L. Marquez-Gomez, Lily R. Torp, Lily Gao and Pamela Peralta-Yahya

Biosensors 2023, 13(6), 571; https://doi.org/10.3390/bios13060571 - 23 May 2023

Viewed by 1498

Abstract

Histamine receptor 2 (HR_H2) blockers are used to treat peptic ulcers and gastric reflux. Chlorquinaldol and chloroxine, which contain an 8-hydroxyquinoline (8HQ) core, have recently been identified as blocking HR_H2. To gain insight into the mode of action of 8HQ-based blockers, here, we leverage an HR_H2-based sensor in yeast to evaluate the role of key residues in the HR_H2 active site on histamine and 8HQ-based blocker binding. We find that the HR_H2 mutations D98A, F254A, Y182A, and Y250A render the receptor inactive in the presence of histamine, while HR_H2:D186A and HR_H2:T190A retain residual activity. Based on molecular docking studies, this outcome correlates with the ability of the pharmacologically relevant histamine tautomers to interact with D98 via the charged amine. Docking studies also suggest that, unlike established HR_H2 blockers that interact with both ends of the HR_H2 binding site, 8HQ-based blockers interact with only one end, either the end framed by D98/Y250 or T190/D186. Experimentally, we find that chlorquinaldol and chloroxine still inactivate HR_H2:D186A by shifting their engagement from D98 to Y250 in the case of chlorquinaldol and D186 to Y182 in the case of chloroxine. Importantly, the tyrosine interactions are supported by the intramolecular hydrogen bonding of the 8HQ-based blockers. The insight gained in this work will aid in the development of improved HR_H2 therapeutics. More generally, this work demonstrates that Gprotein-coupled receptor (GPCR)-based sensors in yeast can help elucidate the mode of action of novel ligands for GPCRs, a family of receptors that bind 30% of FDA therapeutics. Full article

(This article belongs to the Special Issue Genetically Encoded, Small-Molecule Biosensors and Their Applications)

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Review

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16 pages, 1402 KiB

Open AccessReview

Application of Metabolite-Responsive Biosensors for Plant Natural Products Biosynthesis

by Jianli Zhang, Xinyu Gong, Qi Gan and Yajun Yan

Biosensors 2023, 13(6), 633; https://doi.org/10.3390/bios13060633 - 07 Jun 2023

Cited by 1 | Viewed by 1727

Abstract

Plant natural products (PNPs) have shown various pharmaceutical activities, possessing great potential in global markets. Microbial cell factories (MCFs) provide an economical and sustainable alternative for the synthesis of valuable PNPs compared with traditional approaches. However, the heterologous synthetic pathways always lack native regulatory systems, bringing extra burden to PNPs production. To overcome the challenges, biosensors have been exploited and engineered as powerful tools for establishing artificial regulatory networks to control enzyme expression in response to environments. Here, we reviewed the recent progress involved in the application of biosensors that are responsive to PNPs and their precursors. Specifically, the key roles these biosensors played in PNP synthesis pathways, including isoprenoids, flavonoids, stilbenoids and alkaloids, were discussed in detail. Full article

(This article belongs to the Special Issue Genetically Encoded, Small-Molecule Biosensors and Their Applications)

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14 pages, 1864 KiB

Open AccessReview

Applications and Tuning Strategies for Transcription Factor-Based Metabolite Biosensors

by Gloria J. Zhou and Fuzhong Zhang

Biosensors 2023, 13(4), 428; https://doi.org/10.3390/bios13040428 - 28 Mar 2023

Cited by 3 | Viewed by 2570

Abstract

Transcription factor (TF)-based biosensors are widely used for the detection of metabolites and the regulation of cellular pathways in response to metabolites. Several challenges hinder the direct application of TF-based sensors to new hosts or metabolic pathways, which often requires extensive tuning to achieve the optimal performance. These tuning strategies can involve transcriptional or translational control depending on the parameter of interest. In this review, we highlight recent strategies for engineering TF-based biosensors to obtain the desired performance and discuss additional design considerations that may influence a biosensor’s performance. We also examine applications of these sensors and suggest important areas for further work to continue the advancement of small-molecule biosensors. Full article

(This article belongs to the Special Issue Genetically Encoded, Small-Molecule Biosensors and Their Applications)

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