ArticleChemistry & biology2015
Target-based identification of whole-cell active inhibitors of biotin biosynthesis in Mycobacterium tuberculosis.
Article in Chemistry & biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Structure-Guided Development of a Potent BioA Inhibitor Validates Biotin Synthesis Inhibition as a Therapeutic Strategy for Tuberculosis.bioRxiv : the preprint server for biology · 2025Article
- ScreeningOpen research Europe · 2025Article
- Advances and prospects in microbial production of biotin.Microbial cell factories · 2024Review
- Unrealized targets in the discovery of antibiotics for Gram-negative bacterial infections.Nature reviews. Drug discovery · 2023Review
- Screening for small molecule inhibitors of SAH nucleosidase using an SAH riboswitch.Analytical biochemistry · 2023Article
- Three enigmatic BioH isoenzymes are programmed in the early stage of mycobacterial biotin synthesis, an attractive anti-TB drug target.PLoS pathogens · 2022Article
- Phenotypic screening of compound libraries as a platform for the identification of antibiotic adjuvants: Identification of colistin adjuvants from a natural product library.Methods in enzymology · 2022Article
- Insights into the molecular determinants involved inVirulence · 2021Review
- Discovery of quinolone derivatives as antimycobacterial agents.RSC advances · 2021Article
- Synthesis of the Hexahydropyrrolo-[3,2-c]-quinoline Core Structure and Strategies for Further Elaboration to Martinelline, Martinellic Acid, Incargranine B, and Seneciobipyrrolidine.Molecules (Basel, Switzerland) · 2021Review
- Towards the sustainable discovery and development of new antibiotics.Nature reviews. Chemistry · 2021Review
- Tuberculosis Drug Discovery: A Decade of Hit Assessment for Defined Targets.Frontiers in cellular and infection microbiology · 2021Review
- The primary step of biotin synthesis in mycobacteria.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The quest for the holy grail: new antitubercular chemical entities, targets and strategies.Drug discovery today · 2020Review
- Theory and applications of differential scanning fluorimetry in early-stage drug discovery.Biophysical reviews · 2020Review
- Mimicking the human environment in mice reveals that inhibiting biotin biosynthesis is effective against antibiotic-resistant pathogens.Nature microbiology · 2020Article
- The Biotin Biosynthetic Pathway in Mycobacterium tuberculosis is a Validated Target for the Development of Antibacterial Agents.Current medicinal chemistry · 2020Review
- A single regulator NrtR controls bacterial NADeLife · 2019Article
- Functional Replacement of the BioC and BioH Proteins of Escherichia coli Biotin Precursor Biosynthesis by Ehrlichia chaffeensis Novel Proteins.Current microbiology · 2019Article
- Chemical probes and drug leads from advances in synthetic planning and methodology.Nature reviews. Drug discovery · 2018Review
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12 authors.
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Abstract
Biotin biosynthesis is essential for survival and persistence of Mycobacterium tuberculosis (Mtb) in vivo. The aminotransferase BioA, which catalyzes the antepenultimate step in the biotin pathway, has been established as a promising target due to its vulnerability to chemical inhibition. We performed high-throughput screening (HTS) employing a fluorescence displacement assay and identified a diverse set of potent inhibitors including many diversity-oriented synthesis (DOS) scaffolds. To efficiently select only hits targeting biotin biosynthesis, we then deployed a whole-cell counterscreen in biotin-free and biotin-containing medium against wild-type Mtb and in parallel with isogenic bioA Mtb strains that possess differential levels of BioA expression. This counterscreen proved crucial to filter out compounds whose whole-cell activity was off target as well as identify hits with weak, but measurable whole-cell activity in BioA-depleted strains. Several of the most promising hits were cocrystallized with BioA to provide a framework for future structure-based drug design efforts.
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