Mycobacterial biotin synthases require an auxiliary protein to convert dethiobiotin into biotin Journal Article
| Authors: | Qu, D.; Ge, P.; Botella, L.; Park, S. W.; Lee, H. N.; Thornton, N.; Bean, J. M.; Krieger, I. V.; Sacchettini, J. C.; Ehrt, S.; Aldrich, C. C.; Schnappinger, D. |
| Article Title: | Mycobacterial biotin synthases require an auxiliary protein to convert dethiobiotin into biotin |
| Abstract: | Lipid biosynthesis in the pathogen Mycobacterium tuberculosis depends on biotin for posttranslational modification of key enzymes. However, the mycobacterial biotin synthetic pathway is not fully understood. Here, we show that rv1590, a gene of previously unknown function, is required by M. tuberculosis to synthesize biotin. Chemical–generic interaction experiments mapped the function of rv1590 to the conversion of dethiobiotin to biotin, which is catalyzed by biotin synthases (BioB). Biochemical studies confirmed that in contrast to BioB of Escherichia coli, BioB of M. tuberculosis requires Rv1590 (which we named “biotin synthase auxiliary protein” or BsaP), for activity. We found homologs of bsaP associated with bioB in many actinobacterial genomes, and confirmed that BioB of Mycobacteriumsmegmatis also requires BsaP. Structural comparisons of BsaP-associated biotin synthases with BsaP-independent biotin synthases suggest that the need for BsaP is determined by the [2Fe–2S] cluster that inserts sulfur into dethiobiotin. Our findings open new opportunities to seek BioB inhibitors to treat infections with M. tuberculosis and other pathogens. © The Author(s) 2024. |
| Keywords: | controlled study; gene deletion; genetics; nonhuman; comparative study; metabolism; complex formation; gene expression; steady state; protein; protein binding; in vitro study; enzymology; bacterial strain; bacterial protein; mycobacterium tuberculosis; bacterial proteins; amino acid sequence; protein synthesis; escherichia coli; immunoblotting; genome; protein structure; bacterium culture; bacterium; tuberculosis; transposon; biotin; bacterial gene; mycobacterium smegmatis; dissociation constant; antimicrobial activity; equilibrium constant; transcription factor pax5; article; whole genome sequencing; desthiobiotin; biotin synthase; sulfurtransferases; sulfurtransferase |
| Journal Title: | Nature Communications |
| Volume: | 15 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-05-16 |
| Start Page: | 4161 |
| Language: | English |
| DOI: | 10.1038/s41467-024-48448-1 |
| PUBMED: | 38755122 |
| PROVIDER: | scopus |
| PMCID: | PMC11099021 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
