Phenol sensor (DmpR + CRISPRa)

Detects phenol and methylphenols in water/soil. The DmpR aromatic sensor gates a CRISPRa circuit driving a fluorescent reporter, in the phenol-tolerant chassis P. putida KT2440.

Environmental contaminantBSL-1 chassistemplatephenolaromaticpollutantwatersoilenvironmentalCRISPRa
Input
Phenol / (methyl)phenols
Environmental contaminant
Sense
CRISPRa-activation
dCas9-ω (CRISPRa activator)
Chassis
Pseudomonas putida KT2440
BSL-1
Output
sfGFP
fluorescent

What it detects

Analyte
Phenol / (methyl)phenols — DmpR responds across µM phenol
Category
Environmental contaminant
Signal
Phenolic pollutants in industrial effluent and contaminated water

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
DmpR is a sigma-54-dependent activator that binds phenol effectors and activates the Po promoter.
Signal flow
Phenol -> DmpR activates Po -> transcribes an sgRNA -> dCas9-activator amplifies a fluorescent reporter (CRISPRa) -> fluorescence rises with phenol.

Safe chassis

Pseudomonas putida KT2440Pseudomonas putida

A certified safety-strain soil bacterium with exceptional solvent/stress tolerance and diverse metabolism. The premier chassis for environmental biosensing of pollutants and heavy metals in soil and water.

BSL-1

Genetic parts

PartRoleSource / id
DmpR regulator
Phenol/2-methylphenol-responsive activator.
regulatorPseudomonas dmp operon (sigma-54 activator)
Po promoter
Activated by effector-bound DmpR.
promoterdmp operon promoter
Reporter-activating sgRNAsgRNAdesigned for CRISPRa 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 (field fluorimeter)
Positive result
Fluorescence increases with phenol concentration.

Performance

Limit of detection
DmpR module: µM phenol (module-validated).
Dynamic range
~1-100 µM phenol
Response time
~180 min
Device validated
No — design template (parts validated individually)

DmpR aromatic sensing and CRISPRa are validated separately; integrated device is a design template. P. putida natively tolerates aromatics.

Safety

Biosafety level
BSL-1 (non-pathogenic chassis)
GRAS chassis
No
Biocontainment
P. putida KT2440 certified HV1 safety host; add containment for field use.
Field-deployable
Yes (with containment)

Phenol-tolerant chassis works in real contaminated samples.

Build & run

#StageStep
1designDesign CRISPRa sgRNA
Target a weak reporter promoter; check host off-targets.
2assemblyAssemble units
TU1: DmpR + Po -> sgRNA. TU2: dCas9-omega. TU3: weak promoter -> sfGFP. SEVA vectors.
3transformationTransform P. putida KT2440
Electroporate; select; confirm phenol-dependent activation.
4inductionExpose to sample
Add water/soil eluate + phenol standard curve.
5readoutMeasure fluorescence
Interpolate phenol from the curve.

Source & parts

Design
Design template combining the DmpR phenol-sensing module with P. putida CRISPRa
Parts validated in
  • Shingler et al. / DmpR phenol sensing (Pseudomonas dmp)
  • Bikard et al. 2013, NAR (CRISPRa)
License
Parts per their original sources; design template CC BY 4.0