Targeting Mycobacterium tuberculosis F₄₂₀-dependent dehydrogenases for new anti-tubercular drug discovery

The bacillus Mycobacterium tuberculosis (Mtb) is the aetiological agent of the devastating disease of man, called tuberculosis (TB). Till date, it has remained a major public health problem especially in the global South where significant mortalities are recorded annually due to poverty, poor treatment compliance, emergence of different forms of drug-resistant cases, and human immunodeficiency virus (HIV) co-infection. Managing this disease requires the development of new anti-mycobacterial agents. Here, the potential of targeting a group of Mtb enzymes that utilize the rare deazaflavin cofactor, F₄₂₀, for new anti-tubercular drug discovery using fragment-based drug discovery (FBDD) approaches is reviewed. Additionally, this review looks into the merits and demerits of the various recombinant protein expression systems that can be employed for the production of these enzymes.