Dehydrosqualene synthase (CrtM) (CrtM)

Staphylococcus aureus dehydrosqualene synthase (CrtM) is an essential enzyme involved in the biosynthesis of staphyloxanthin, the golden carotenoid pigment that serves as a key virulence factor for S. aureus (Liu, G. Y., et al., 2005, Science). The enzyme facilitates the head-to-head condensation of two farnesyl pyrophosphate (FPP) molecules to form dehydrosqualene, marking the first committed step in the pigment's production (Liu, C. I., et al., 2008, Science). Staphyloxanthin acts as an antioxidant, protecting the pathogen from the oxidative burst (reactive oxygen species) employed by host neutrophils to kill bacteria (UniProt, P0A1P1). Targeting CrtM is a recognized anti-virulence strategy; inhibiting the enzyme does not kill the bacteria directly but renders them vulnerable to the host's innate immune system (Liu, C. I., et al., 2008, Science). This approach is particularly attractive for treating multidrug-resistant strains like MRSA, as it places less selective pressure on the bacteria to develop resistance compared to traditional antibiotics (Song, Y., et al., 2009, Journal of Medicinal Chemistry). However, because CrtM shares structural homology with human squalene synthase, therapeutic agents must be carefully designed to ensure selectivity and avoid disrupting human cholesterol metabolism (Liu, C. I., et al., 2008, Science).

Other names

4,4'-diapophytoene synthaseStaphyloxanthin biosynthesis protein CrtMSqualene synthase-like protein

Inhibition of dehydrosqualene synthase blocks the production of the antioxidant pigment staphyloxanthin, increasing bacterial susceptibility to host immune-mediated oxidative stress (Liu, C. I., et al., 2008, Science).