L-aspartate 1-decarboxylase (PanD) (PanD)

L-aspartate 1-decarboxylase (PanD) is an essential bacterial enzyme that catalyzes the decarboxylation of L-aspartate to produce beta-alanine, a key precursor in the biosynthesis of pantothenate (Vitamin B5) and Coenzyme A (CoA) (UniProt P9WNS5). CoA is a fundamental cofactor required for numerous metabolic processes, including the tricarboxylic acid (TCA) cycle and the synthesis and degradation of fatty acids (PubMed: 23934124). Since humans do not possess the PanD enzyme and instead acquire Vitamin B5 from dietary sources, this enzyme is a highly specific target for antimicrobial development, particularly against Mycobacterium tuberculosis (PubMed: 25157117). The anti-tuberculosis drug pyrazinamide (PZA) functions as a pro-drug that is converted by the bacteria into pyrazinoic acid (POA), which subsequently targets and inhibits PanD (PubMed: 24812211). This inhibition leads to a critical depletion of CoA levels, disrupting the metabolic homeostasis of the pathogen and contributing to the sterilization of persistent bacterial populations (PubMed: 23934124). Mutations in the panD gene are a recognized mechanism of resistance to pyrazinamide, highlighting the enzyme's clinical relevance in treating drug-resistant tuberculosis (PubMed: 25157117).

Other names

Aspartate 1-decarboxylaseADCPanDL-aspartate alpha-decarboxylaseAspartate decarboxylase

Pyrazinoic acid, the active metabolite of pyrazinamide, binds to L-aspartate 1-decarboxylase (PanD) and inhibits its enzymatic activity, preventing the synthesis of beta-alanine and subsequently depleting Coenzyme A (CoA) levels (PubMed: 23934124, PubMed: 25157117).