| Enediyne antitumor antibiotic maduropeptin biosynthesis featuring a C-methyltransferase that acts on a CoA-tethered aromatic substrate. | |
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MedLine Citation:
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PMID: 20718468 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The enediyne antitumor antibiotic maduropeptin (MDP) is produced by Actinomadura madurae ATCC 39144. The biosynthetic pathway for the 3,6-dimethylsalicylic acid moiety of the MDP chromophore is proposed to be comprised of four enzymes: MdpB, MdpB1, MdpB2, and MdpB3. Based on the previously characterized biosynthesis of the naphthoic acid moiety of neocarzinostatin (NCS), we expected a biosynthetic pathway featuring carboxylic acid activation by the MdpB2 CoA ligase immediately before its coupling to an enediyne core intermediate. Surprisingly, the MDP aromatic acid biosynthetic pathway employs an unusual logic in which MdpB2-catalyzed CoA activation occurs before MdpB1-catalyzed C-methylation, demonstrating that MdpB1 is apparently unique in its ability to C-methylate a CoA-tethered aromatic acid. MdpB2 is a promiscuous CoA ligase capable of activating a variety of salicylic acid analogues, a property that could be potentially exploited to engineer MDP analogues. |
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Authors:
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Jianya Ling; Geoffrey P Horsman; Sheng-Xiong Huang; Yinggang Luo; Shuangjun Lin; Ben Shen |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of the American Chemical Society Volume: 132 ISSN: 1520-5126 ISO Abbreviation: J. Am. Chem. Soc. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-08 Completed Date: 2011-01-05 Revised Date: 2013-05-28 |
Medline Journal Info:
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Nlm Unique ID: 7503056 Medline TA: J Am Chem Soc Country: United States |
Other Details:
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Languages: eng Pagination: 12534-6 Citation Subset: IM |
Affiliation:
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Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Actinobacteria
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enzymology,
metabolism Biocatalysis Coenzyme A Ligases / metabolism* Enediynes / chemistry, metabolism* Methyltransferases / metabolism* Molecular Structure Stereoisomerism Substrate Specificity |
| Grant Support | |
ID/Acronym/Agency:
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CA113297/CA/NCI NIH HHS; CA78747/CA/NCI NIH HHS; R01 CA078747/CA/NCI NIH HHS; R01 CA078747-10/CA/NCI NIH HHS; R01 CA078747-10S1/CA/NCI NIH HHS; U19 CA113297/CA/NCI NIH HHS; U19 CA113297-05/CA/NCI NIH HHS; U19 CA113297-050001/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enediynes; 0/maduropeptin enediyne; EC 2.1.1.-/Methyltransferases; EC 6.2.1.-/Coenzyme A Ligases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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