Mycobacterium tuberculosis coenzyme A biosynthesis pathway enzymes (Mtb CoA pathway)

The Mycobacterium tuberculosis coenzyme A (CoA) biosynthesis pathway is a collection of essential enzymes responsible for the de novo synthesis of CoA, a fundamental cofactor for bacterial metabolism [1]. This pathway is vital for the production of mycolic acids, which are essential components of the mycobacterial cell wall, and for the operation of the tricarboxylic acid cycle [2]. Key enzymes in this metabolic route include pantothenate synthetase (PanC), aspartate 1-decarboxylase (PanD), and pantothenate kinase (CoaA) [3]. These enzymes are considered high-priority therapeutic targets because they are essential for bacterial survival and often possess structural features distinct from their human counterparts, allowing for selective inhibition [4]. For example, the anti-tuberculosis drug pyrazinamide is known to target PanD, leading to a reduction in CoA levels and subsequent bacterial death [5]. Research into this pathway continues to identify novel inhibitors, such as pantothenamides, which aim to overcome existing drug resistance by targeting these critical metabolic steps [6]. [1] Spry, C., et al. (2008). Coenzyme A biosynthesis: an antimicrobial drug target. FEMS Microbiology Reviews. [2] Cole, S. T., et al. (1998). Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. [3] Zheng, R., et al. (2013). The enzymes of the pantothenate and coenzyme A biosynthesis pathways in Mycobacterium tuberculosis. Frontiers in Bioscience. [4] Leonardi, R., et al. (2005). Coenzyme A: back in fashion. Progress in Lipid Research. [5] Shi, W., et al. (2014). Pyrazinamide inhibits PanD (aspartate 1-decarboxylase) in Mycobacterium tuberculosis. Science. [6] Evans, J. C., et al. (2016). The Mycobacterium tuberculosis Pantothenate Biosynthesis Pathway: A Source of Targets for Antituberculosis Drug Development. Antibiotics.

Other names

Mycobacterium tuberculosis coenzyme A biosynthesis pathwayMtb CoA biosynthesis pathwayPantothenate and coenzyme A biosynthesis pathwayMtb pantothenate pathway

Inhibition of enzymes within the coenzyme A biosynthetic pathway, resulting in the depletion of intracellular CoA levels, which disrupts mycolic acid synthesis and energy metabolism, ultimately leading to bacterial cell death.