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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
20
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pubmed:dateCreated |
2001-5-15
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pubmed:abstractText |
The rifamycin synthetase is primed with a 3-amino-5-hydroxybenzoate starter unit by a loading module that contains domains homologous to the adenylation and thiolation domains of nonribosomal peptide synthetases. Adenylation and thiolation activities of the loading module were reconstituted in vitro and shown to be independent of coenzyme A, countering literature proposals that the loading module is a coenzyme A ligase. Kinetic parameters for covalent arylation of the loading module were measured directly for the unnatural substrates benzoate and 3-hydroxybenzoate. This analysis was extended through competition experiments to determine the relative rates of incorporation of a series of substituted benzoates. Our results show that the loading module can accept a variety of substituted benzoates, although it exhibits a preference for the 3-, 5-, and 3,5-disubstituted benzoates that most closely resemble its biological substrate. The considerable substrate tolerance of the loading module of rifamycin synthetase suggests that the module has potential as a tool for generating substituted derivatives of natural products.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-amino-5-hydroxybenzoic acid,
http://linkedlifedata.com/resource/pubmed/chemical/3-hydroxybenzoate coenzyme A ligase,
http://linkedlifedata.com/resource/pubmed/chemical/3-hydroxybenzoic acid,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Monophosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Aminobenzoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Benzoates,
http://linkedlifedata.com/resource/pubmed/chemical/Coenzyme A Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Holoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxybenzoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Rifamycins
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0006-2960
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
22
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6116-23
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11352749-Actinomycetales,
pubmed-meshheading:11352749-Adenosine Monophosphate,
pubmed-meshheading:11352749-Amino Acid Motifs,
pubmed-meshheading:11352749-Aminobenzoic Acids,
pubmed-meshheading:11352749-Benzoates,
pubmed-meshheading:11352749-Coenzyme A Ligases,
pubmed-meshheading:11352749-Genetic Vectors,
pubmed-meshheading:11352749-Holoenzymes,
pubmed-meshheading:11352749-Hydroxybenzoic Acids,
pubmed-meshheading:11352749-Kinetics,
pubmed-meshheading:11352749-Multienzyme Complexes,
pubmed-meshheading:11352749-Peptide Synthases,
pubmed-meshheading:11352749-Protein Structure, Tertiary,
pubmed-meshheading:11352749-Rifamycins,
pubmed-meshheading:11352749-Substrate Specificity
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pubmed:year |
2001
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pubmed:articleTitle |
The loading module of rifamycin synthetase is an adenylation-thiolation didomain with substrate tolerance for substituted benzoates.
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pubmed:affiliation |
Departments of Chemical Engineering, Chemistry, and Biochemistry, Stanford University, Stanford, California 94305-5025, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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