Nitrate sensor (NarL + CRISPRi)

Detects nitrate in water and food. The native E. coli NarX/NarL nitrate two-component system gates a CRISPRa circuit driving a fluorescent reporter, in safe E. coli K-12.

Chemical / metaboliteBSL-1 chassistemplatenitratechemicalwater-qualityfood-safetyCRISPRa
Input
Nitrate (NO3-)
Chemical / metabolite
Sense
CRISPRa-activation
dCas9-ω (CRISPRa activator)
Chassis
E. coli K-12 (MG1655)
BSL-1
Output
sfGFP
fluorescent

What it detects

Analyte
Nitrate (NO3-) — NarX/NarL responds across µM-mM nitrate
Category
Chemical / metabolite
Signal
Nitrate in drinking water, agricultural runoff, and cured foods

Genetic circuit

⤢ click to enlarge

Genetic construct (SBOL)

The DNA construct as transcription units, drawn with SBOL Visual part glyphs.

⤢ click to enlarge

CRISPR sensing mechanism

Strategy
CRISPRa-activation · amplifier logic
Cas protein
dCas9-ω (CRISPRa activator)
Analyte sensor
The NarX sensor kinase phosphorylates NarL in response to nitrate; phospho-NarL activates the nitrate-responsive Pnar promoter.
Signal flow
NO3- -> NarX/NarL activates Pnar -> transcribes an sgRNA -> dCas9-activator amplifies a weak reporter promoter (CRISPRa) -> green fluorescence rises with nitrate.

Safe chassis

E. coli K-12 (MG1655)Escherichia coli

The non-pathogenic laboratory workhorse. K-12 strains have lost the ability to colonize the human gut and are the reference BSL-1 host for genetic engineering, with the deepest tooling of any bacterial chassis.

BSL-1

Genetic parts

PartRoleSource / id
NarX/NarL two-component system
Endogenous nitrate sensor; no porting needed in E. coli.
regulatorNative E. coli nar regulon
Pnar promoter (e.g. PnarG)
Activated by phospho-NarL under nitrate.
promoterE. coli narGHJI promoter
Reporter-activating sgRNA
Transcribed from Pnar.
sgRNAdesigned upstream of a weak reporter promoter
sgRNA scaffold (SpCas9)
GTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGC
sgRNAStandard SpCas9 scaffold
dCas9-ω activatordCas9Bikard et al. 2013 (CRISPRa)
sfGFPreporterPedelacq et al. 2006

Output & readout

Type
fluorescent
Reporter
sfGFP
Readout
Green fluorescence (plate reader / field fluorimeter)
Positive result
Fluorescence increases with nitrate concentration.

Performance

Limit of detection
NarX/NarL module reports nitrate over µM-mM (module-validated).
Dynamic range
~10 µM - 10 mM nitrate
Response time
~120 min
Device validated
No — design template (parts validated individually)

Uses E. coli's native nitrate sensor (anaerobic/microaerobic induction); CRISPRa amplifier integration is a design template. Note Pnar is also FNR/oxygen-modulated.

Safety

Biosafety level
BSL-1 (non-pathogenic chassis)
GRAS chassis
No
Biocontainment
Lab/contained; add kill-switch for field use.
Field-deployable
Yes (with containment)

E. coli K-12 non-pathogenic BSL-1 host; relevant to drinking-water and food-safety nitrate limits.

Build & run

#StageStep
1designDesign CRISPRa sgRNA
Target the activation window of a weak reporter promoter; verify host off-targets.
2assemblyAssemble units
TU1: Pnar -> sgRNA (NarX/NarL endogenous). TU2: dCas9-omega. TU3: weak promoter -> sfGFP.
3transformationTransform E. coli K-12
Select; confirm nitrate-dependent activation and low background.
4inductionExpose to sample
Incubate (micro-aerobically) with the sample + nitrate standard curve.
5readoutMeasure fluorescence
Interpolate nitrate from the curve.

Source & parts

Design
Design template combining E. coli's native NarX/NarL nitrate sensor with a dCas9 CRISPRa reporter
Parts validated in
  • Stewart 1993 / E. coli nar regulon literature (NarX/NarL nitrate sensing)
  • Bikard et al. 2013, NAR (CRISPRa)
License
Parts per their original sources; design template CC BY 4.0