In vivo biosensors: mechanisms, development, and applications

  • Shuobo Shi
  • Ee Lui AngEmail author
  • Huimin ZhaoEmail author
Metabolic Engineering and Synthetic Biology - Original Paper


In vivo biosensors can recognize and respond to specific cellular stimuli. In recent years, biosensors have been increasingly used in metabolic engineering and synthetic biology, because they can be implemented in synthetic circuits to control the expression of reporter genes in response to specific cellular stimuli, such as a certain metabolite or a change in pH. There are many types of natural sensing devices, which can be generally divided into two main categories: protein-based and nucleic acid-based. Both can be obtained either by directly mining from natural genetic components or by engineering the existing genetic components for novel specificity or improved characteristics. A wide range of new technologies have enabled rapid engineering and discovery of new biosensors, which are paving the way for a new era of biotechnological progress. Here, we review recent advances in the design, optimization, and applications of in vivo biosensors in the field of metabolic engineering and synthetic biology.


Biosensor Metabolic engineering Synthetic biology Metabolite sensing 



Analog-to-digital converter


Alcohol dehydrogenase




Cis-aconitate decarboxylase gene


Cis,cis-muconic acid


Cytidine deaminase


(2′-5′,3′-5′) Cyclic guanosine monophosphate-adenosine monophosphate


Capillary electrophoresis


Cyan fluorescent protein


Customized optimization of metabolic pathways by combinatorial transcriptional engineering


3,5-Difluoro-4-hydroxybenzylidene imidazolinone


3,4-Dihydroxy benzoate




Dynamic sensor-regulator system


Error-prone PCR


Fluorescence activated cell sorting


Cytosine deaminase gene


Free fatty acid


Fluorescence intensity


Fluorescent proteins


Farnesyl pyrophosphate


Feedback-regulated evolution of phenotype


Förster resonance energy transfer


Genes for the environment, membranes, and motility


Green fluorescent protein


Glucosamine 6-phosphate


N-acetyl glucosamine


Citrate synthetase gene


G-protein-coupled receptors


Hammerhead ribozyme




Histidine kinase


3-Hydroxy propionic acid






α-Ketoglutarate dehydrogenase


Lysine-binding periplasmic protein


LysR-type transcriptional regulator


Multiplex automated genome engineering


Maltase gene


Metabolite-binding protein


Methionine-binding protein






N-acetyl-l-glutamate kinase


N-acetylneuramine acid


N-methyl mesoporphyrin IX


O-acetyl homoserine


O-acetyl serine


Periplasmic-binding proteins


Population quality control


Quorum sensing


RNAi-assisted genome evolution


Ribosome binding site


Repressor, open reading frame, kinase


Response regulator






Sensor-assisted transcriptional regulator engineering


Streptavidin-binding aptamer


Systematic evolution of ligands by exponential enrichment






Tricarboxylic acid


Two-component system


Transcriptional factor


Trehalose repressor


Trackable multiplex recombineering


Yellow fluorescent protein


Yeast oligo-mediated genome engineering


Zinc finger



We acknowledge funding supports from the State Key Laboratory of Microbial Technology Open Projects Fund in China (Project no. M2017-02 to S.S.), the National Research Foundation Singapore (NRF2013-THE001-095 to E.L.A.), and the Visiting Investigator Programme of Agency for Science, Technology, and Research, Singapore and US Department of Energy (DE-SC0018260 to H.Z.).


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Copyright information

© Society for Industrial Microbiology and Biotechnology 2018

Authors and Affiliations

  1. 1.Metabolic Engineering Research Laboratory, Science and Engineering InstitutesAgency for Science, Technology and ResearchSingaporeSingapore
  2. 2.Beijing Advanced Innovation Center for Soft Matter Science and EngineeringBeijing University of Chemical TechnologyBeijingPeople’s Republic of China
  3. 3.Department of Chemical and Biomolecular EngineeringUniversity of Illinois at Urbana-ChampaignUrbanaUSA

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