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In vivo biosensors: mechanisms, development, and applications

  • Shuobo Shi
  • Ee Lui Ang
  • Huimin Zhao
Metabolic Engineering and Synthetic Biology - Original Paper

Abstract

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.

Keywords

Biosensor Metabolic engineering Synthetic biology Metabolite sensing 

Abbreviations

ADC

Analog-to-digital converter

ADH

Alcohol dehydrogenase

1,4-BDO

1,4-Butanediol

CAD

Cis-aconitate decarboxylase gene

CCM

Cis,cis-muconic acid

CDA

Cytidine deaminase

2′,3′-cGAMP

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

CE

Capillary electrophoresis

CFP

Cyan fluorescent protein

COMPACTER

Customized optimization of metabolic pathways by combinatorial transcriptional engineering

DFHBI

3,5-Difluoro-4-hydroxybenzylidene imidazolinone

34DHB

3,4-Dihydroxy benzoate

l-DOPA

l-3,4-Dihydroxyphenylalanine

DSRS

Dynamic sensor-regulator system

epPCR

Error-prone PCR

FACS

Fluorescence activated cell sorting

fcy1

Cytosine deaminase gene

FFA

Free fatty acid

FI

Fluorescence intensity

FP

Fluorescent proteins

FPP

Farnesyl pyrophosphate

FREP

Feedback-regulated evolution of phenotype

FRET

Förster resonance energy transfer

GEMM

Genes for the environment, membranes, and motility

GFP

Green fluorescent protein

GlcN6P

Glucosamine 6-phosphate

GlcNAc

N-acetyl glucosamine

gltA

Citrate synthetase gene

GPCR

G-protein-coupled receptors

HHR

Hammerhead ribozyme

Hi-Fi

High-fidelity

HK

Histidine kinase

3-HP

3-Hydroxy propionic acid

IL

Interleukin

IPTG

Isopropyl-beta-d-thiogalactopyranoside

α-KGDH

α-Ketoglutarate dehydrogenase

LAO

Lysine-binding periplasmic protein

LTTR

LysR-type transcriptional regulator

MAGE

Multiplex automated genome engineering

malQ

Maltase gene

MBP

Metabolite-binding protein

MetN

Methionine-binding protein

MT

Metallothionein

MVA

Mevalonate

NAGK

N-acetyl-l-glutamate kinase

NeuAC

N-acetylneuramine acid

NMM

N-methyl mesoporphyrin IX

OAH

O-acetyl homoserine

OAS

O-acetyl serine

PBP

Periplasmic-binding proteins

PopQC

Population quality control

QS

Quorum sensing

RAGE

RNAi-assisted genome evolution

RBS

Ribosome binding site

ROK

Repressor, open reading frame, kinase

RR

Response regulator

SAM

S-adenosylmethionine

SAH

S-adenosyl-l-homocysteine

SATRE

Sensor-assisted transcriptional regulator engineering

SBA

Streptavidin-binding aptamer

SELEX

Systematic evolution of ligands by exponential enrichment

T6P

Trehalose-6-phosphate

Tc

Tetracycline

TCA

Tricarboxylic acid

TCS

Two-component system

TF

Transcriptional factor

TreR

Trehalose repressor

TRMR

Trackable multiplex recombineering

YFP

Yellow fluorescent protein

YOGE

Yeast oligo-mediated genome engineering

ZF

Zinc finger

Notes

Acknowledgements

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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