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Bacterial metabolic enzymes in Propionibacterium acnes (now reclassified as Cutibacterium acnes) comprise a diverse array of proteins essential for the bacterium's survival, colonization, and pathogenicity within the human skin's pilosebaceous unit (Scholz & Kilian, 2016). Key enzymes include secreted triacylglycerol lipases, such as GehA, which hydrolyze sebum triglycerides into pro-inflammatory free fatty acids, and hyaluronate lyases (Hyl), which degrade host extracellular matrix components to facilitate tissue invasion (Falcocchio et al., 2006; Nazipi et al., 2017). Additionally, enzymes involved in the porphyrin biosynthesis pathway produce metabolites that trigger host inflammatory responses and oxidative stress (Barnard et al., 2020). Other critical metabolic targets include the folate synthesis pathway, involving dihydropteroate synthase and dihydrofolate reductase, and fatty acid synthesis enzymes like beta-ketoacyl acyl carrier protein synthase III (KAS III) (Hooton, 2003; Kum et al., 2016). These enzymes are central to the pathogenesis of acne vulgaris, as their metabolic activities promote follicular hyperkeratosis and sustain the inflammatory environment characteristic of the disease. Therapeutic interventions target these enzymes through various mechanisms, including the use of traditional antibiotics to inhibit protein or folate synthesis, and the development of specific inhibitors to block lipase activity or porphyrin production.
Inhibition of bacterial protein synthesis (30S/50S ribosome), inhibition of folate biosynthesis (DHPS/DHFR), inhibition of triacylglycerol lipase activity, inhibition of fatty acid synthesis (KAS III), and oxidative disruption of bacterial metabolic pathways.
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