Document Detail


Genetic and chemical characterization of ibuprofen degradation by Sphingomonas Ibu-2.
MedLine Citation:
PMID:  23329679     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Sphingomonas Ibu-2 has the unusual ability to cleave the acid side chain from the pharmaceutical ibuprofen and related arylacetic acid derivatives to yield corresponding catechols under aerobic conditions via a previously uncharacterized mechanism. Screening a chromosomal library of Ibu-2 DNA in Escherichia coli EPI300 allowed us to identify one fosmid clone (pFOS3G7) that conferred the ability to metabolize ibuprofen to isobutylcatechol. Characterization of pFOS3G7 loss-of-function transposon mutants permitted identification of five ORFs, ipfABDEF, whose predicted amino acid sequences bore similarity to the large and small units of an aromatic dioxygenase (ipfAB), a sterol carrier protein X (SCPx) thiolase (ipfD), a domain of unknown function 35 (DUF35) protein (ipfE) and an aromatic CoA ligase (ipfF). Two additional ORFs, ipfH and ipfI, which encode putative ferredoxin reductase and ferredoxin components of an aromatic dioxygenase system, respectively, were also identified on pFOS3G7. Complementation of a markerless loss-of-function ipfD deletion mutant restored catechol production as did complementation of the ipfF Tn mutant. Expression of subcloned ipfABDEF alone in E. coli did not impart full metabolic activity unless coexpressed with ipfHI. CoA ligation followed by ring oxidation is common to phenylacetic acid pathways. However, the need for a putative SCPx thiolase (IpfD) and DUF35 protein (IpfE) in aerobic arylacetic acid degradation is unprecedented. This work provides preliminary insights into the mechanism behind this novel arylacetic acid-deacylating, catechol-generating activity.
Authors:
Robert W Murdoch; Anthony G Hay
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-17
Journal Detail:
Title:  Microbiology (Reading, England)     Volume:  159     ISSN:  1465-2080     ISO Abbreviation:  Microbiology (Reading, Engl.)     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-07     Completed Date:  2013-08-19     Revised Date:  2014-08-05    
Medline Journal Info:
Nlm Unique ID:  9430468     Medline TA:  Microbiology     Country:  England    
Other Details:
Languages:  eng     Pagination:  621-32     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
GENBANK/EF090268
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MeSH Terms
Descriptor/Qualifier:
Biotransformation
Catechols / metabolism
DNA, Bacterial / chemistry,  genetics
Escherichia coli / genetics
Gene Deletion
Genetic Complementation Test
Ibuprofen / metabolism*
Metabolic Networks and Pathways / genetics*
Molecular Sequence Data
Sequence Analysis, DNA
Sphingomonas / metabolism*
Grant Support
ID/Acronym/Agency:
ES 07052-27/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Catechols; 0/DNA, Bacterial; LF3AJ089DQ/catechol; WK2XYI10QM/Ibuprofen
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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