Phytoene synthase (PSY)

Phytoene synthase (PSY) is a pivotal enzyme in the carotenoid biosynthetic pathway, responsible for catalyzing the head-to-head condensation of two molecules of geranylgeranyl pyrophosphate (GGPP) to produce 15-cis-phytoene (UniProt: P27457). As the rate-limiting step in carotenoid production in plants and many microorganisms, it is a primary target for agricultural biotechnology and metabolic engineering, most notably in the development of Golden Rice to mitigate Vitamin A deficiency in developing nations (Science, 2000, 287:303-305). While humans lack this enzyme, making it an attractive target for herbicides and anti-infectives, it is structurally similar to human squalene synthase, which poses a challenge for pharmacological selectivity (PNAS, 2008, 105:20440-20445). In the context of human health, research has focused on targeting bacterial orthologs of PSY, such as CrtM or CrtB, which produce carotenoid pigments like staphyloxanthin in Staphylococcus aureus. These pigments protect bacteria from oxidative burst by host immune cells; thus, inhibiting PSY-like enzymes can serve as an anti-virulence strategy to sensitize pathogens to the host immune system (Journal of Medicinal Chemistry, 2010, 53:4876-4890). Small-molecule inhibitors like BPH-652 have demonstrated efficacy in experimental models, highlighting the target's potential in treating multi-drug resistant infections without directly exerting selective pressure for antibiotic resistance.

Other names

15-cis-phytoene synthaseGeranylgeranyl-diphosphate geranylgeranyltransferaseCrtBPSY1PSY2PSY3Dehydrosqualene synthase-like enzyme

Inhibition of the head-to-head condensation of two molecules of geranylgeranyl pyrophosphate (GGPP) to form the C40 hydrocarbon phytoene, which is the first committed step in the carotenoid biosynthetic pathway (UniProt: P27457; PubMed: 20438181).