Aspartokinase (ASK) (ASK)

Mycobacterium tuberculosis aspartate kinase (ASK), also known as aspartokinase, is a critical enzyme that catalyzes the first step of the aspartate biosynthetic pathway [2, 8]. This pathway is responsible for producing essential proteinogenic amino acids, including lysine, threonine, methionine, and isoleucine, as well as diaminopimelate, a vital component of the mycobacterial cell wall [1, 31]. ASK is feedback-inhibited by threonine, and its deregulation or inhibition leads to metabolic imbalances, such as the toxic accumulation of homoserine and lysine, which are bactericidal to both actively growing and persistent M. tuberculosis [1, 18]. Because the aspartate pathway is entirely absent in humans, ASK represents a highly attractive and selective therapeutic target for the development of new anti-tuberculosis drugs [3, 21]. Current research focuses on identifying small-molecule inhibitors that can disrupt this pathway to eradicate chronic and drug-resistant infections [7, 26].

Other names

Aspartate kinasebeta-aspartokinaseRv3709cMTV025.057c

Inhibition of the first committed step of the aspartate pathway, which prevents the biosynthesis of essential amino acids (lysine, threonine, methionine, isoleucine) and the cell wall precursor diaminopimelate, leading to bacterial death and clearance of persistent infections [1, 3].