bims-mricoa 2022-09-18 papers

Issue of 2022–09–18
three papers selected by
Merve Yavuz, Bilkent University

ACS Synth Biol. 2022 Sep 12.

Intestinal Engineered Probiotics as Living Therapeutics: Chassis Selection, Colonization Enhancement, Gene Circuit Design, and Biocontainment.

Yan Huang, Xiaojun Lin, Siyang Yu, Ruiyue Chen, Weizhao Chen.

Intestinal probiotics are often used for the in situ treatment of diseases, such as metabolic disorders, tumors, and chronic inflammatory infections. Recently, there has been an increased emphasis on intelligent, customized treatments with a focus on long-term efficacy; however, traditional probiotic therapy has not kept up with this trend. The use of synthetic biology to construct gut-engineered probiotics as live therapeutics is a promising avenue in the treatment of specific diseases, such as phenylketonuria and inflammatory bowel disease. These studies generally involve a series of fundamental design issues: choosing an engineered chassis, improving the colonization ability of engineered probiotics, designing functional gene circuits, and ensuring the safety of engineered probiotics. In this review, we summarize the relevant past research, the progress of current research, and discuss the key issues that restrict the widespread application of intestinal engineered probiotic living therapeutics.

Keywords: biocontainment; colonization improvement; engineered probiotics; functional gene circuits; living therapeutics; synthetic biology

DOI: https://doi.org/10.1021/acssynbio.2c00314

Front Bioeng Biotechnol. 2022 ;10 938056

Surveying the Genetic Design Space for Transcription Factor-Based Metabolite Biosensors: Synthetic Gamma-Aminobutyric Acid and Propionate Biosensors in E. coli Nissle 1917.

Matthew Lebovich, Lauren B Andrews.

Engineered probiotic bacteria have been proposed as a next-generation strategy for noninvasively detecting biomarkers in the gastrointestinal tract and interrogating the gut-brain axis. A major challenge impeding the implementation of this strategy has been the difficulty to engineer the necessary whole-cell biosensors. Creation of transcription factor-based biosensors in a clinically-relevant strain often requires significant tuning of the genetic parts and gene expression to achieve the dynamic range and sensitivity required. Here, we propose an approach to efficiently engineer transcription-factor based metabolite biosensors that uses a design prototyping construct to quickly assay the gene expression design space and identify an optimal genetic design. We demonstrate this approach using the probiotic bacterium Escherichia coli Nissle 1917 (EcN) and two neuroactive gut metabolites: the neurotransmitter gamma-aminobutyric acid (GABA) and the short-chain fatty acid propionate. The EcN propionate sensor, utilizing the PrpR transcriptional activator from E. coli, has a large 59-fold dynamic range and >500-fold increased sensitivity that matches biologically-relevant concentrations. Our EcN GABA biosensor uses the GabR transcriptional repressor from Bacillus subtilis and a synthetic GabR-regulated promoter created in this study. This work reports the first known synthetic microbial whole-cell biosensor for GABA, which has an observed 138-fold activation in EcN at biologically-relevant concentrations. Using this rapid design prototyping approach, we engineer highly functional biosensors for specified in vivo metabolite concentrations that achieve a large dynamic range and high output promoter activity upon activation. This strategy may be broadly useful for accelerating the engineering of metabolite biosensors for living diagnostics and therapeutics.

Keywords: depression; gamma-aminobutyric acid (GABA); genetically encoded biosensor; gut microbial metabolites; living therapeutics; neurotransmitter; propionate; whole cell biosensor

DOI: https://doi.org/10.3389/fbioe.2022.938056

ACS Appl Mater Interfaces. 2022 Sep 13.

Aligned Magnetic Nanocomposites for Modularized and Recyclable Soft Microrobots.

Langquan Shui, Ke Ni, Zhengzhi Wang.

Creating reconfigurable and recyclable soft microrobots that can execute multimodal locomotion has been a challenge due to the difficulties in material processing and structure engineering at a small scale. Here, we propose a facile technique to manufacture diverse soft microrobots (∼100 μm in all dimensions) by mechanically assembling modular magnetic microactuators into different three-dimensional (3D) configurations. The module is composed of a cubic micropillar supported on a square substrate, both made of elastomer matrix embedded with prealigned magnetic nanoparticle chains. By directionally bonding the sides or backs of identical modules together, we demonstrate that assemblies from only two and four modules can execute a wide range of locomotion, including gripping microscale objects, crawling and crossing solid obstacles, swimming within narrow and tortuous microchannels, and rolling along flat and inclined surfaces, upon applying proper magnetic fields. The assembled microrobots can additionally perform pick-transfer-place and cargo-release tasks at the microscale. More importantly, like the game of block-building, the microrobots can be disassembled back to separate modules and then reassembled to other configurations as demanded. The present study not only provides a versatile and economic manufacturing technique for reconfigurable and recyclable soft microrobots, enabling unlimited design space for diverse robotic locomotion from limited materials and module structures, but also extends the functionality and dexterity of existing soft robots to microscale that should facilitate practical applications at such small scale.

Keywords: elastomer nanocomposites; magnetic actuation; modular assembly; multimodal locomotivity; soft robotics

DOI: https://doi.org/10.1021/acsami.2c13108