Abstract
Mycobacterium tuberculosis, responsible for Tuberculosis (TB), remains the leading
cause of mortality among infectious diseases worldwide from a single infectious agent, with an estimated
1.7 million deaths in 2016. Biotin is an essential cofactor in M. tuberculosis that is required
for lipid biosynthesis and gluconeogenesis. M. tuberculosis relies on de novo biotin biosynthesis to
obtain this vital cofactor since it cannot scavenge sufficient biotin from a mammalian host. The biotin
biosynthetic pathway in M. tuberculosis has been well studied and rigorously genetically validated
providing a solid foundation for medicinal chemistry efforts. This review examines the mechanism
and structure of the enzymes involved in biotin biosynthesis and ligation, summarizes the reported
genetic validation studies of the pathway, and then analyzes the most promising inhibitors
and natural products obtained from structure-based drug design and phenotypic screening.
Keywords:
Tuberculosis, infectious disease, Mycobacterium tuberculosis, biotin, biosynthesis, enzymology, antibiotics.
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