| pubmed-article:12230561 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12230561 | lifeskim:mentions | umls-concept:C1113686 | lld:lifeskim |
| pubmed-article:12230561 | lifeskim:mentions | umls-concept:C0051581 | lld:lifeskim |
| pubmed-article:12230561 | lifeskim:mentions | umls-concept:C0164369 | lld:lifeskim |
| pubmed-article:12230561 | pubmed:issue | 18 | lld:pubmed |
| pubmed-article:12230561 | pubmed:dateCreated | 2002-9-16 | lld:pubmed |
| pubmed-article:12230561 | pubmed:abstractText | Semi-synthetic cephalosporin antibiotics belong to the top 10 of most sold drugs, and are produced from 7-aminodesacetoxycephalosporanic acid (7-ADCA). Recently new routes have been developed which allow for the production of adipyl-7-ADCA by a novel fermentation process. To complete the biosynthesis of 7-ADCA a highly active adipyl acylase is needed for deacylation of the adipyl derivative. Such an adipyl acylase can be generated from known glutaryl acylases. The glutaryl acylase of Pseudomonas SY-77 was mutated in a first round by exploration mutagenesis. For selection the mutants were grown on an adipyl substrate. The residues that are important to the adipyl acylase activity were identified, and in a second round saturation mutagenesis of this selected stretch of residues yielded variants with a threefold increased catalytic efficiency. The effect of the mutations could be rationalized on hindsight by the 3D structure of the acylase. In conclusion, the substrate specificity of a dicarboxylic acid acylase was shifted towards adipyl-7-ADCA by a two-step directed evolution strategy. Although derivatives of the substrate were used for selection, mutants retained activity on the beta-lactam substrate. The strategy herein described may be generally applicable to all beta-lactam acylases. | lld:pubmed |
| pubmed-article:12230561 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12230561 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12230561 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:12230561 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12230561 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12230561 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12230561 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12230561 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12230561 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12230561 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12230561 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:12230561 | pubmed:issn | 0014-2956 | lld:pubmed |
| pubmed-article:12230561 | pubmed:author | pubmed-author:QuaxWim JWJ | lld:pubmed |
| pubmed-article:12230561 | pubmed:author | pubmed-author:van der... | lld:pubmed |
| pubmed-article:12230561 | pubmed:author | pubmed-author:VerhaertRaymo... | lld:pubmed |
| pubmed-article:12230561 | pubmed:author | pubmed-author:SioCharles... | lld:pubmed |
| pubmed-article:12230561 | pubmed:author | pubmed-author:RiemensAnja... | lld:pubmed |
| pubmed-article:12230561 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12230561 | pubmed:volume | 269 | lld:pubmed |
| pubmed-article:12230561 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12230561 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12230561 | pubmed:pagination | 4495-504 | lld:pubmed |
| pubmed-article:12230561 | pubmed:dateRevised | 2007-7-23 | lld:pubmed |
| pubmed-article:12230561 | pubmed:meshHeading | pubmed-meshheading:12230561... | lld:pubmed |
| pubmed-article:12230561 | pubmed:meshHeading | pubmed-meshheading:12230561... | lld:pubmed |
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| pubmed-article:12230561 | pubmed:meshHeading | pubmed-meshheading:12230561... | lld:pubmed |
| pubmed-article:12230561 | pubmed:meshHeading | pubmed-meshheading:12230561... | lld:pubmed |
| pubmed-article:12230561 | pubmed:meshHeading | pubmed-meshheading:12230561... | lld:pubmed |
| pubmed-article:12230561 | pubmed:meshHeading | pubmed-meshheading:12230561... | lld:pubmed |
| pubmed-article:12230561 | pubmed:year | 2002 | lld:pubmed |
| pubmed-article:12230561 | pubmed:articleTitle | Directed evolution of a glutaryl acylase into an adipyl acylase. | lld:pubmed |
| pubmed-article:12230561 | pubmed:affiliation | Pharmaceutical Biology, University Centre for Pharmacy, Groningen, the Netherlands; DSM-Gist, Delft, The Netherlands. | lld:pubmed |
| pubmed-article:12230561 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12230561 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:12230561 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:12230561 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:12230561 | lld:pubmed |
