Anaerobic biosynthesis of the lower ligand of vitamin B12
Identifieur interne : 000046 ( Pmc/Curation ); précédent : 000045; suivant : 000047Anaerobic biosynthesis of the lower ligand of vitamin B12
Auteurs : Amrita B. Hazra ; Andrew W. Han ; Angad P. Mehta ; Kenny C. Mok ; Vadim Osadchiy ; Tadhg P. Begley ; Michiko E. TagaSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2015.
Abstract
Vitamin B12 is required by humans and a variety of other organisms for diverse metabolic processes, but is produced only by a subset of microorganisms. The anaerobic biosynthesis of the “lower ligand” of B12, 5,6-dimethylbenzimidazole (DMB), is the only unknown component of the B12 biosynthetic pathway. We report the identification of the
Url:
DOI: 10.1073/pnas.1509132112
PubMed: 26246619
PubMed Central: 4553811
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<author><name sortKey="Hazra, Amrita B" sort="Hazra, Amrita B" uniqKey="Hazra A" first="Amrita B." last="Hazra">Amrita B. Hazra</name>
<affiliation><nlm:aff id="aff1">Department of Plant and Microbial Biology,<institution>University of California, Berkeley</institution>
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<author><name sortKey="Osadchiy, Vadim" sort="Osadchiy, Vadim" uniqKey="Osadchiy V" first="Vadim" last="Osadchiy">Vadim Osadchiy</name>
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<author><name sortKey="Taga, Michiko E" sort="Taga, Michiko E" uniqKey="Taga M" first="Michiko E." last="Taga">Michiko E. Taga</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Anaerobic biosynthesis of the lower ligand of vitamin B<sub>12</sub>
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<author><name sortKey="Hazra, Amrita B" sort="Hazra, Amrita B" uniqKey="Hazra A" first="Amrita B." last="Hazra">Amrita B. Hazra</name>
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<author><name sortKey="Han, Andrew W" sort="Han, Andrew W" uniqKey="Han A" first="Andrew W." last="Han">Andrew W. Han</name>
<affiliation><nlm:aff id="aff1">Department of Plant and Microbial Biology,<institution>University of California, Berkeley</institution>
,<addr-line>CA</addr-line>
94720;</nlm:aff>
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<author><name sortKey="Mehta, Angad P" sort="Mehta, Angad P" uniqKey="Mehta A" first="Angad P." last="Mehta">Angad P. Mehta</name>
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, College Station,<addr-line>TX</addr-line>
77843</nlm:aff>
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<author><name sortKey="Mok, Kenny C" sort="Mok, Kenny C" uniqKey="Mok K" first="Kenny C." last="Mok">Kenny C. Mok</name>
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,<addr-line>CA</addr-line>
94720;</nlm:aff>
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<author><name sortKey="Osadchiy, Vadim" sort="Osadchiy, Vadim" uniqKey="Osadchiy V" first="Vadim" last="Osadchiy">Vadim Osadchiy</name>
<affiliation><nlm:aff id="aff1">Department of Plant and Microbial Biology,<institution>University of California, Berkeley</institution>
,<addr-line>CA</addr-line>
94720;</nlm:aff>
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<author><name sortKey="Begley, Tadhg P" sort="Begley, Tadhg P" uniqKey="Begley T" first="Tadhg P." last="Begley">Tadhg P. Begley</name>
<affiliation><nlm:aff id="aff2">Department of Chemistry,<institution>Texas A&M University</institution>
, College Station,<addr-line>TX</addr-line>
77843</nlm:aff>
</affiliation>
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<author><name sortKey="Taga, Michiko E" sort="Taga, Michiko E" uniqKey="Taga M" first="Michiko E." last="Taga">Michiko E. Taga</name>
<affiliation><nlm:aff id="aff1">Department of Plant and Microbial Biology,<institution>University of California, Berkeley</institution>
,<addr-line>CA</addr-line>
94720;</nlm:aff>
</affiliation>
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<series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title>
<idno type="ISSN">0027-8424</idno>
<idno type="eISSN">1091-6490</idno>
<imprint><date when="2015">2015</date>
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<front><div type="abstract" xml:lang="en"><title>Significance</title>
<p>Vitamin B<sub>12</sub>
is required by humans and a variety of other organisms for diverse metabolic processes, but is produced only by a subset of microorganisms. The anaerobic biosynthesis of the “lower ligand” of B<sub>12</sub>
, 5,6-dimethylbenzimidazole (DMB), is the only unknown component of the B<sub>12</sub>
biosynthetic pathway. We report the identification of the <italic>bzaABCDE</italic>
genes that are necessary and sufficient for the anaerobic biosynthesis of DMB. We have characterized the role of each of the <italic>bza</italic>
genes and identified three intermediates in the pathway. This finding not only completes the B<sub>12</sub>
biosynthesis pathway but also enables the sequence-based prediction of cobamides synthesized by anaerobic microorganisms.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id>
<journal-id journal-id-type="iso-abbrev">Proc. Natl. Acad. Sci. U.S.A</journal-id>
<journal-id journal-id-type="hwp">pnas</journal-id>
<journal-id journal-id-type="pmc">pnas</journal-id>
<journal-id journal-id-type="publisher-id">PNAS</journal-id>
<journal-title-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title>
</journal-title-group>
<issn pub-type="ppub">0027-8424</issn>
<issn pub-type="epub">1091-6490</issn>
<publisher><publisher-name>National Academy of Sciences</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">26246619</article-id>
<article-id pub-id-type="pmc">4553811</article-id>
<article-id pub-id-type="publisher-id">201509132</article-id>
<article-id pub-id-type="doi">10.1073/pnas.1509132112</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject>
<subj-group><subject>Microbiology</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Anaerobic biosynthesis of the lower ligand of vitamin B<sub>12</sub>
</article-title>
<alt-title alt-title-type="short">Anaerobic biosynthesis of the lower ligand of B<sub>12</sub>
</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Hazra</surname>
<given-names>Amrita B.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Han</surname>
<given-names>Andrew W.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="author-notes" rid="fn1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mehta</surname>
<given-names>Angad P.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mok</surname>
<given-names>Kenny C.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Osadchiy</surname>
<given-names>Vadim</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Begley</surname>
<given-names>Tadhg P.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Taga</surname>
<given-names>Michiko E.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>2</sup>
</xref>
</contrib>
<aff id="aff1"><sup>a</sup>
Department of Plant and Microbial Biology,<institution>University of California, Berkeley</institution>
,<addr-line>CA</addr-line>
94720;</aff>
<aff id="aff2"><sup>b</sup>
Department of Chemistry,<institution>Texas A&M University</institution>
, College Station,<addr-line>TX</addr-line>
77843</aff>
</contrib-group>
<author-notes><corresp id="cor1"><sup>2</sup>
To whom correspondence should be addressed. Email: <email>taga@berkeley.edu</email>
.</corresp>
<fn fn-type="edited-by"><p>Edited by E. Peter Greenberg, University of Washington, Seattle, WA, and approved July 1, 2015 (received for review May 9, 2015)</p>
</fn>
<fn fn-type="con"><p>Author contributions: A.B.H., A.W.H., K.C.M., T.P.B., and M.E.T. designed research; A.B.H., A.W.H., A.P.M., K.C.M., V.O., and M.E.T. performed research; A.B.H., A.W.H., A.P.M., K.C.M., V.O., and M.E.T. analyzed data; and A.B.H. and M.E.T. wrote the paper.</p>
</fn>
<fn fn-type="present-address" id="fn1"><p><sup>1</sup>
Present address: Second Genome, Inc., South San Francisco, CA 94080.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><day>25</day>
<month>8</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epub"><day>5</day>
<month>8</month>
<year>2015</year>
</pub-date>
<volume>112</volume>
<issue>34</issue>
<fpage>10792</fpage>
<lpage>10797</lpage>
<self-uri xlink:title="pdf" xlink:href="pnas.201509132.pdf"></self-uri>
<abstract abstract-type="executive-summary"><title>Significance</title>
<p>Vitamin B<sub>12</sub>
is required by humans and a variety of other organisms for diverse metabolic processes, but is produced only by a subset of microorganisms. The anaerobic biosynthesis of the “lower ligand” of B<sub>12</sub>
, 5,6-dimethylbenzimidazole (DMB), is the only unknown component of the B<sub>12</sub>
biosynthetic pathway. We report the identification of the <italic>bzaABCDE</italic>
genes that are necessary and sufficient for the anaerobic biosynthesis of DMB. We have characterized the role of each of the <italic>bza</italic>
genes and identified three intermediates in the pathway. This finding not only completes the B<sub>12</sub>
biosynthesis pathway but also enables the sequence-based prediction of cobamides synthesized by anaerobic microorganisms.</p>
</abstract>
<abstract><p>Vitamin B<sub>12</sub>
(cobalamin) is required by humans and other organisms for diverse metabolic processes, although only a subset of prokaryotes is capable of synthesizing B<sub>12</sub>
and other cobamide cofactors. The complete aerobic and anaerobic pathways for the de novo biosynthesis of B<sub>12</sub>
are known, with the exception of the steps leading to the anaerobic biosynthesis of the lower ligand, 5,6-dimethylbenzimidazole (DMB). Here, we report the identification and characterization of the complete pathway for anaerobic DMB biosynthesis. This pathway, identified in the obligate anaerobic bacterium <italic>Eubacterium limosum</italic>
, is composed of five previously uncharacterized genes, <italic>bzaABCDE</italic>
, that together direct DMB production when expressed in anaerobically cultured <italic>Escherichia coli</italic>
. Expression of different combinations of the <italic>bza</italic>
genes revealed that 5-hydroxybenzimidazole, 5-methoxybenzimidazole, and 5-methoxy-6-methylbenzimidazole, all of which are lower ligands of cobamides produced by other organisms, are intermediates in the pathway. The <italic>bza</italic>
gene content of several bacterial and archaeal genomes is consistent with experimentally determined structures of the benzimidazoles produced by these organisms, indicating that these genes can be used to predict cobamide structure. The identification of the <italic>bza</italic>
genes thus represents the last remaining unknown component of the biosynthetic pathway for not only B<sub>12</sub>
itself, but also for three other cobamide lower ligands whose biosynthesis was previously unknown. Given the importance of cobamides in environmental, industrial, and human-associated microbial metabolism, the ability to predict cobamide structure may lead to an improved ability to understand and manipulate microbial metabolism.</p>
</abstract>
<kwd-group><kwd>vitamin B<sub>12</sub>
</kwd>
<kwd>cobalamin</kwd>
<kwd>cobamide</kwd>
<kwd>5,6-dimethylbenzimidazole</kwd>
<kwd>biosynthesis</kwd>
</kwd-group>
<funding-group><award-group id="gs1"><funding-source id="sp1">National Science Foundation (NSF)<named-content content-type="funder-id">100000001</named-content>
</funding-source>
<award-id rid="sp1">MCB1122046</award-id>
</award-group>
</funding-group>
<counts><page-count count="6"></page-count>
</counts>
</article-meta>
</front>
</pmc>
</record>
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