Siskos, Alexandros P. ; Baerga-Ortiz, Abel ; Bali, Shilpa ; Stein, Viktor ; Mamdani, Hassan ; Spiteller, Dieter ; Popovic, Bojana ; Spencer, Jonathan B. ; Staunton, James ; Weissman, Kira J. ; Leadlay, Peter F. (2005)
Molecular basis of Celmer's rules: stereochemistry of catalysis by isolated ketoreductase domains from modular polyketide synthases.
In: Chemistry & biology, 12 (10)
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
A system is reported for the recombinant expression of individual ketoreductase (KR) domains from modular polyketide synthases (PKSs) and scrutiny of their intrinsic specificity and stereospecificity toward surrogate diketide substrates. The eryKR(1) and the tylKR(1) domains, derived from the first extension module of the erythromycin PKS and the tylosin PKS, respectively, both catalyzed reduction of (2R, S)-2-methyl-3-oxopentanoic acid N-acetylcysteamine thioester, with complete stereoselectivity and stereospecificity, even though the substrate is not tethered to an acyl carrier protein or an intact PKS multienzyme. In contrast, and to varying degrees, the isolated enzymes eryKR(2), eryKR(5), and eryKR(6) exercised poorer control over substrate selection and the stereochemical course of ketoreduction. These data, together with modeling of diketide binding to KR(1) and KR(2), demonstrate the fine energetic balance between alternative modes of presentation of ketoacylthioester substrates to KR active sites.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2005 |
| Autor(en): | Siskos, Alexandros P. ; Baerga-Ortiz, Abel ; Bali, Shilpa ; Stein, Viktor ; Mamdani, Hassan ; Spiteller, Dieter ; Popovic, Bojana ; Spencer, Jonathan B. ; Staunton, James ; Weissman, Kira J. ; Leadlay, Peter F. |
| Art des Eintrags: | Bibliographie |
| Titel: | Molecular basis of Celmer's rules: stereochemistry of catalysis by isolated ketoreductase domains from modular polyketide synthases. |
| Sprache: | Englisch |
| Publikationsjahr: | 2005 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Chemistry & biology |
| Jahrgang/Volume einer Zeitschrift: | 12 |
| (Heft-)Nummer: | 10 |
| Kurzbeschreibung (Abstract): | A system is reported for the recombinant expression of individual ketoreductase (KR) domains from modular polyketide synthases (PKSs) and scrutiny of their intrinsic specificity and stereospecificity toward surrogate diketide substrates. The eryKR(1) and the tylKR(1) domains, derived from the first extension module of the erythromycin PKS and the tylosin PKS, respectively, both catalyzed reduction of (2R, S)-2-methyl-3-oxopentanoic acid N-acetylcysteamine thioester, with complete stereoselectivity and stereospecificity, even though the substrate is not tethered to an acyl carrier protein or an intact PKS multienzyme. In contrast, and to varying degrees, the isolated enzymes eryKR(2), eryKR(5), and eryKR(6) exercised poorer control over substrate selection and the stereochemical course of ketoreduction. These data, together with modeling of diketide binding to KR(1) and KR(2), demonstrate the fine energetic balance between alternative modes of presentation of ketoacylthioester substrates to KR active sites. |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Protein Engineering of Ion Conducting Nanopores |
| Hinterlegungsdatum: | 14 Nov 2016 11:58 |
| Letzte Änderung: | 14 Nov 2016 11:58 |
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