Target intelligence / Profile preview

Dehydrosqualene desaturase (CrtN) (CrtN)

Target
CrtN
Molecular classification
Enzyme, Oxidoreductase
01

Overview

Dehydrosqualene desaturase (CrtN) is an essential enzyme in the biosynthetic pathway of staphyloxanthin, the hallmark golden pigment of Staphylococcus aureus (UniProt P0A1P1). This enzyme catalyzes the oxidative desaturation of dehydrosqualene into 4,4'-diaponeurosporene, a precursor to the final antioxidant product. Staphyloxanthin plays a critical role in bacterial pathogenesis by neutralizing reactive oxygen species (ROS) produced by host neutrophils, thereby allowing the bacteria to evade the innate immune response (Liu et al., 2005). Because CrtN is required for pigment production but not for basic bacterial growth, it represents an attractive anti-virulence target. Inhibiting CrtN renders S. aureus susceptible to immune clearance, providing a strategy to treat infections, including those caused by methicillin-resistant S. aureus (MRSA), while potentially minimizing the development of antibiotic resistance (Chen et al., 2016). Experimental inhibitors like naftifine have demonstrated the potential of this approach by reducing bacterial load in vivo without exerting direct bactericidal pressure (Gao et al., 2017).

Other names
4,4'-diapophytoene desaturaseDiapophytoene desaturaseCrtNDehydrosqualene desaturase
02

Mechanism of action

Inhibition of the oxidative desaturation of dehydrosqualene to 4,4'-diaponeurosporene, thereby blocking the production of the antioxidant pigment staphyloxanthin (Chen et al., 2016).

03

Biological functions

Carotenoid biosynthesisStaphyloxanthin biosynthesisAntioxidant defenseVirulence
04

Disease associations

Infection
05

Safety considerations

Potential off-target effects on human cholesterol biosynthesis enzymesLimited efficacy as a monotherapy requiring functional host immunity
06

Interacting drugs

Naftifine

2 more in the full profile.

07

Biomarkers

Staphyloxanthin levelsBacterial pigmentationSensitivity to reactive oxygen species

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