| Title: |
Mycobacterial biotin synthases require an auxiliary protein to convert dethiobiotin into biotin. |
| Authors: |
Qu, Di, Ge, Peng, Botella, Laure, Park, Sae Woong, Lee, Ha-Na, Thornton, Natalie, Bean, James M., Krieger, Inna V., Sacchettini, James C., Ehrt, Sabine, Aldrich, Courtney C., Schnappinger, Dirk |
| Source: |
Nature Communications; 5/16/2024, Vol. 15 Issue 1, p1-11, 11p |
| Subject Terms: |
BIOTIN, SYNTHASES, POST-translational modification, MYCOBACTERIUM tuberculosis, PROTEINS, GLYCOLIPIDS |
| 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. Lipid biosynthesis in the pathogen M. tuberculosis depends on biotin for posttranslational modification of key enzymes. Here, Qu et al. identify an auxiliary protein that is required by M. tuberculosis to synthesize biotin. [ABSTRACT FROM AUTHOR] |
|
Copyright of Nature Communications is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |
