Catalyzes the pyruvoyl-dependent decarboxylation of aspartate to produce beta-alanine. Overexpression of wild-type protein confers resistance to pyrazinoic acid (POA), the active form of the anti-tuberculosis prodrug pyrazinamide (PZA). H(+) + L-aspartate = beta-alanine + CO2 Binds 1 pyruvoyl group covalently per subunit. kcat is 0.65 sec(-1), specific activity 2100 nmol/min/mg for L-aspartate. Cofactor biosynthesis; (R)-pantothenate biosynthesis; beta-alanine from L-aspartate: step 1/1. Heterooctamer of four alpha and four beta subunits. Is synthesized initially as an inactive proenzyme, which is activated by self-cleavage at a specific serine bond to produce a beta-subunit with a hydroxyl group at its C-terminus and an alpha-subunit with a pyruvoyl group at its N-terminus. Cleavage is not necessary for tetramerization upon expression in E.coli; protein expressed in E.coli is fully process in vitro after 48 hours at 37 degrees Celsius (PubMed:12182836). Simultaneous disruption of panD and panC gives a mutant unable to grow in the absence of panothenate. The double mutant has a highly attenuated disease response in BALB/c and SCID mice; immunocompromised BALB/c SCID mice survive on average 36 weeks as opposed to 5 weeks for mice infected with wild-type bacteria, while immunocompetent BALB/c mice survive indefinitely. In wild-type mice bacteria grow for 3 weeks then undergo a steady decline, bacteria persist over 8 months in SCID mice (PubMed:12219086). The double mutant is sensitive to PZA but not POA in liquid culture, beta-alanine but not pantothenate antagonize the effect of PZA at pH 5.8 (PubMed:25246400). Subcutaneous immunization with the double panD and panC bacterial disruption mutant protects mice for over a year against subsequent virulent M.tuberculosis (strain Erdman) infections; mice show mild lung inflammation and fibrosis despite a chronic bacterila infection. This is a promising attenuated vaccine strain. Pantothenate, pantetheine and beta-alanine containing compounds (all part of the panthothenate/coenzyme A biosynthetic pathway) antagonize PZA and POA antitubercular activity. However cultivation of the double panD and panC mutant with low levels of pantetheine (an intermediate between pantothenate and coenzyme A, at pH 5.8) restores sensitivity to PZA, suggesting PanD is not the PZA target. Belongs to the PanD family.