Abstract：
:Biotin plays an essential role in growth of mycobacteria. Synthesis of the cofactor is essential for Mycobacterium tuberculosis to establish and maintain chronic infections in a murine model of tuberculosis. Although the late steps of mycobacterial biotin synthesis, assembly of the heterocyclic rings, are thought to follow the canonical pathway, the mechanism of synthesis of the pimelic acid moiety that contributes most of the biotin carbon atoms is unknown. We report that the Mycobacterium smegmatis gene annotated as encoding Tam, an O-methyltransferase that monomethylates and detoxifies trans-aconitate, instead encodes a protein having the activity of BioC, an O-methyltransferase that methylates the free carboxyl of malonyl-ACP. The M. smegmatis Tam functionally replaced Escherichia coli BioC both in vivo and in vitro. Moreover, deletion of the M. smegmatis tam gene resulted in biotin auxotrophy, and addition of biotin to M. smegmatis cultures repressed tam gene transcription. Although its pathogenicity precluded in vivo studies, the M. tuberculosis Tam also replaced E. coli BioC both in vivo and in vitro and complemented biotin-independent growth of the M. smegmatis tam deletion mutant strain. Based on these data, we propose that the highly conserved mycobacterial tam genes be renamed bioCM. tuberculosis BioC presents a target for antituberculosis drugs which thus far have been directed at late reactions in the pathway with some success.
journal_name
Proc Natl Acad Sci U S Aauthors
Hu Z,Cronan JEdoi
10.1073/pnas.2010189117subject
Has Abstractpub_date
2020-09-22 00:00:00pages
23794-23801issue
38eissn
0027-8424issn
1091-6490pii
2010189117journal_volume
117pub_type
杂志文章abstract：:Recent evidence suggests that the microbial community in the human intestine may play an important role in the pathogenesis of obesity. We examined 184,094 sequences of microbial 16S rRNA genes from PCR amplicons by using the 454 pyrosequencing technology to compare the microbial community structures of 9 individuals,...
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doi：10.1073/pnas.0812600106
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abstract：:This paper describes experiments in which cytosolic Ca2+ concentrations ([Ca2+]i) and catecholamine release were measured in two populations of chromaffin cells stimulated with a solution enriched in K+ (100 mM). Once depolarized, external Ca2+ or Ba2+ ions were offered to cells either as a single 2.5 mM step or as a ...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
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doi：10.1073/pnas.90.8.3284
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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doi：10.1073/pnas.87.20.7944
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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更新日期：2010-06-22 00:00:00
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更新日期：2017-05-16 00:00:00
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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更新日期：2011-02-01 00:00:00
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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journal_title：Proceedings of the National Academy of Sciences of the United States of America
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doi：10.1073/pnas.2004445117
更新日期：2020-08-25 00:00:00
