The biotin biosynthetic pathway in mycobacterium tuberculosis is a validated target for the development of antibacterial agents

Matthew R. Bockman, Neeraj Mishra, Courtney C. Aldrich

Research output: Contribution to journalReview article

Abstract

Mycobacterium tuberculosis, responsible for Tuberculosis (TB), remains the leading cause of mortality among infectious diseases worldwide from a single infectious agent, with an es-timated 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 bio-tin 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 re-ported 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.

Original languageEnglish (US)
Pages (from-to)4194-4232
Number of pages39
JournalCurrent medicinal chemistry
Volume27
Issue number25
DOIs
StatePublished - 2020

Keywords

  • Antibi-otics
  • Biosynthesis
  • Biotin
  • Enzymology
  • Infectious disease
  • Mycobacterium tuberculosis
  • Tuberculosis

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