Background: Mycolic acids (MAs) are the characteristic, integral building blocks for the
mycomembrane belonging to the insidious bacterial pathogen Mycobacterium tuberculosis (M.tb).
These C60-C90 long α-alkyl-β-hydroxylated fatty acids provide protection to the tubercle bacilli against
the outside threats, thus allowing its survival, virulence and resistance to the current antibacterial
agents. In the post-genomic era, progress has been made towards understanding the crucial enzymatic
machineries involved in the biosynthesis of MAs in M.tb. However, gaps still remain in the exact role
of the phosphorylation and dephosphorylation of regulatory mechanisms within these systems. To date,
a total of 11 serine-threonine protein kinases (STPKs) are found in M.tb. Most enzymes implicated in
the MAs synthesis were found to be phosphorylated in vitro and/or in vivo. For instance, phosphorylation
of KasA, KasB, mtFabH, InhA, MabA, and FadD32 downregulated their enzymatic activity, while
phosphorylation of VirS increased its enzymatic activity. These observations suggest that the kinases
and phosphatases system could play a role in M.tb adaptive responses and survival mechanisms in the
human host. As the mycobacterial STPKs do not share a high sequence homology to the human’s, there
have been some early drug discovery efforts towards developing potent and selective inhibitors.
Objective: Recent updates to the kinases and phosphatases involved in the regulation of MAs biosynthesis
will be presented in this mini-review, including their known small molecule inhibitors.
Conclusion: Mycobacterial kinases and phosphatases involved in the MAs regulation may serve as a
useful avenue for antitubercular therapy.