Aspartate 1-decarboxylase (PanD)

Aspartate 1-decarboxylase (PanD) is a pyruvoyl-dependent enzyme that catalyzes the decarboxylation of L-aspartate to produce beta-alanine, a key precursor for the biosynthesis of pantothenate (Vitamin B5) and Coenzyme A (CoA) [4, 12, 17]. This enzyme is essential for the growth of various microorganisms, including Mycobacterium tuberculosis and Helicobacter pylori, but is notably absent in humans, who obtain Vitamin B5 through their diet [6, 9]. Consequently, PanD is a significant therapeutic target for antimicrobial agents [9]. It is the primary target of the frontline anti-tuberculosis drug pyrazinamide (PZA), which is converted into its active form, pyrazinoic acid (POA), to inhibit PanD activity and potentially trigger its degradation [1, 11]. Mutations in the panD gene are frequently associated with pyrazinamide resistance in clinical isolates of M. tuberculosis [1, 3]. Research continues to explore PanD as a target for novel antibiotics to combat drug-resistant infections [6, 9]. Its role in energy metabolism and fatty acid synthesis makes it essential for bacterial survival and persistence [1, 17].

Other names

Aspartate alpha-decarboxylaseL-aspartate alpha-decarboxylaseL-aspartate 1-carboxy-lyaseADC

Pyrazinamide acts as a prodrug that is converted to pyrazinoic acid (POA), which inhibits the enzymatic activity of PanD and may also trigger its degradation via the ClpC1-ClpP protease system.