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Unformatted text preview: APPLIED AND ENVIRONMENTAL MICROBIOLOGY, Apr. 1994,p. 1292-1296 Vol. 60,No. 4 0099-2240/94/$04.00+0 Copyright 1994,American SocietyforMicrobiology Microbial Transformation of Ibuprofenby aNocardia Species YIJUN CHEN AND JOHN P.N. ROSAZZA* Division ofMedicinalandNaturalProductsChemistryand CenterforBiocatalysisandBioprocessing, CollegeofPharmacy, UniversityofIowa, Iowa City,Iowa 52242 Received 12October 1993/Accepted 21January 1994 The carboxylic acid functional group of ibuprofen [a-methyl-4-(2-methylpropyl)benzene acetic acid] is reduced to the corresponding alcohol and subsequently esterified to the acetate derivative by cultures of Nocardia speciesstrainNRRL 5646.The alcoholand estermicrobial transformation productswere isolated, and their structures were determined by 'H and 13C nuclear magnetic resonance spectroscopy and mass spectrometry. By derivatizationofsyntheticand microbiologicallyproduced ibuprofenalcoholswithS(+)-O- acetylmandelic acid, nuclear magnetic resonance analysis indicated that the carboxylic acid reductase of Nocardia sp. isR enantioselective, giving alcohol products with an enantiomeric excess of 61.2%. The R enantioselectivityofthecarboxylicacidreductase enzymesystemwas confirmedbyusingcellextractstogether withATP and NADPH inthereductionofisomericibuprofens. Microorganisms and their enzymes have received much attentionandarewidelyusedasaclassofbiocatalyticreagents insyntheticorganicchemistry(5,8,10,14-21,25).Biocatalysts arevaluedfortheirintrinsicabilitiestobindorganicsubstrates andtocatalyzehighlyspecificandselectivereactionsunderthe mildestofreactionconditions.Theseselectivitiesandspecific- itiesarerealizedbecauseofhighlyrigidinteractionsoccurring between the enzyme active siteand the substrate molecule. Usefulbiocatalyticreactionsthathavebeenwelldevelopedto dateincludeavarietyofoxidations,reductions,hydrolyses,and carbon-carbonbond ligations.Enzyme reactionssuchasthose catalyzedbyesterases,forexample,maybeusedeitherhydro- lytically or to synthesize esters, depending on the reaction medium, which may be aqueous ororganicincomposition. Biocatalyticreactionsareparticularlyusefulwhen theymay be used to overcome difficulties encountered in catalysis achieved by the use oftraditional chemical approaches. The reductionofcarboxylicacidsbymicroorganismsisarelatively new biocatalyticreaction thathas notyetbeen widelyexam- inedorexploited.Jezo and Zemek reportedthereductionof aromaticacidstotheircorrespondingbenzaldehydederivatives by actinomycetes (9).Kato etal.,reported the reduction of benzoate to benzyl alcohol by a Nocardia strain (13), and Tsuda etal.described the reduction of2-aryloxyacetic acids (23) and arylpropionates (24) by Glomerella species and Gloeosporium species. Carboxylic acid reduction reactions catalyzed by several additional microorganisms have been describedrecentlybyArfmann andAbraham (1)....
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This note was uploaded on 10/06/2010 for the course ES ES271 taught by Professor Machaut during the Spring '10 term at Colby.
- Spring '10