Lysine sensor (LysG + CRISPRa)

Detects L-lysine — the flagship amino-acid product of C. glutamicum. The native LysG transcriptional sensor (used in the classic pSenLys biosensor) gates a CRISPRa circuit driving a fluorescent reporter, for strain screening and process monitoring.

Chemical / metaboliteBSL-1 chassisGRAStemplatelysineamino-acidbioprocessindustrialchemicalCRISPRa
Input
L-lysine
Chemical / metabolite
Sense
CRISPRa-activation
dCas9-ω (CRISPRa activator)
Chassis
Corynebacterium glutamicum (ATCC 13032)
BSL-1
Output
eYFP
fluorescent

What it detects

Analyte
L-lysine — LysG sensor responds across mM lysine
Category
Chemical / metabolite
Signal
Intracellular/extracellular L-lysine (and basic amino acids) for strain screening and fermentation monitoring

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
LysG (LysR-family) activates the lysE promoter in response to L-lysine (and arginine/histidine).
Signal flow
L-lysine -> LysG activates PlysE -> sgRNA -> dCas9-activator amplifies the reporter (CRISPRa) -> fluorescence rises with lysine. Basis of FACS-based producer screening.

Safe chassis

Corynebacterium glutamicum (ATCC 13032)Corynebacterium glutamicum

A GRAS industrial workhorse used for food-grade amino-acid production at megaton scale. Robust, stress-tolerant, and easy to grow at high density — well suited to industrial-process and chemical monitoring.

BSL-1GRAS · EFSA QPS

Genetic parts

PartRoleSource / id
LysG regulatorregulatorNative C. glutamicum lysG (LysR family); Binder et al. 2012 (pSenLys)
PlysE promoterpromoterC. glutamicum lysE promoter
sgRNAsgRNAdesigned against / upstream of the reporter promoter
sgRNA scaffold (SpCas9)
GTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGC
sgRNAStandard SpCas9 scaffold
dCas9-ω activatordCas9Cleto et al. 2016 (CRISPRi/a in C. glutamicum)
eYFPreporterfluorophore for FACS screening

Output & readout

Type
fluorescent
Reporter
eYFP
Readout
Fluorescence (plate reader / FACS)
Positive result
Fluorescence scales with lysine — enabling single-cell producer screening.

Performance

Device validated
No — design template (parts validated individually)

The LysG/lysE amino-acid biosensor (pSenLys) is validated for FACS-based strain screening; the CRISPRa-amplified version is a design template. Also responds to arginine/histidine.

Safety

Biosafety level
BSL-1 (non-pathogenic chassis)
GRAS chassis
Yes
Biocontainment
Auxotrophic containment; GRAS industrial host.
Field-deployable
Lab / supervised use

GRAS industrial host; bioprocess/QC application.

Build & run

#StageStep
1designDesign sgRNA
Target/position the sgRNA; check C. glutamicum off-targets.
2assemblyAssemble units
Sensor -> sgRNA; dCas9; reporter. Use the host's standard toolkit.
3transformationTransform C. glutamicum
Transform, select, and confirm low background.
4inductionExpose to sample
Incubate with the sample plus a lysine standard curve.
5readoutRead result
Relate signal to concentration.

Source & parts

Design
Design template combining the LysG/lysE lysine biosensor with C. glutamicum CRISPRa
Parts validated in
  • Binder et al. 2012, Genome Biol (LysG/pSenLys amino-acid biosensor)
  • Cleto et al. 2016 (CRISPRi in C. glutamicum)
License
Parts per their original sources; design template CC BY 4.0