A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Chemoenzymatic Synthesis of Novel C-Ribosylated Naphthoquinones
Tekijät: Bastian Blauenburg, Terhi Oja, Karel D Klika, Mikko Metsä-Ketelä
Kustantaja: AMER CHEMICAL SOC
Kustannuspaikka: WASHINGTON; 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
Julkaisuvuosi: 2013
Journal: ACS Chemical Biology
Tietokannassa oleva lehden nimi: Acs Chemical Biology
Lehden akronyymi: ACS Chem.Biol.
Numero sarjassa: 11
Vuosikerta: 8
Numero: 11
Aloitussivu: 2377
Lopetussivu: 2382
Sivujen määrä: 6
ISSN: 1554-8929
DOI: https://doi.org/10.1021/cb400384c
Tiivistelmä
The biological activity of many natural products is dependent on the presence of carbohydrate units, which are usually attached via an O-glycosidic linkage by glycosyltransferases. Recently, an exceptional C-ribosylation event was discovered in the biosynthesis of the polyketide antibiotic alnumycin A. The two-step process involves initial attachment of D-ribose-5-phosphate to the polyaromatic aglycone by the C-glycosynthase AlnA and subsequent dephosphorylation by AlnB, an enzyme of the haloacid dehalogenase family. Here, we tested 23 unnatural substrates to probe the C-ribosylation reaction. The chemoenzymatic synthesis of C-ribosylated juglone, 7-methyl juglone, monomethyl naphthazarin, 8-chloro-7-methyl juglone, and 9-hydroxy-1,4-anthraquinone revealed the importance of a 1,4-quinoid system with an adjacent phenolic ring in order for reaction to occur. To further rationalize the molecular basis for reactivity, factors governing substrate recognition were investigated by NMR binding experiments. Additionally, the suitability of substrates for nucleophilic substitution was assessed by molecular modeling using density functional theory (DFT) calculations.
The biological activity of many natural products is dependent on the presence of carbohydrate units, which are usually attached via an O-glycosidic linkage by glycosyltransferases. Recently, an exceptional C-ribosylation event was discovered in the biosynthesis of the polyketide antibiotic alnumycin A. The two-step process involves initial attachment of D-ribose-5-phosphate to the polyaromatic aglycone by the C-glycosynthase AlnA and subsequent dephosphorylation by AlnB, an enzyme of the haloacid dehalogenase family. Here, we tested 23 unnatural substrates to probe the C-ribosylation reaction. The chemoenzymatic synthesis of C-ribosylated juglone, 7-methyl juglone, monomethyl naphthazarin, 8-chloro-7-methyl juglone, and 9-hydroxy-1,4-anthraquinone revealed the importance of a 1,4-quinoid system with an adjacent phenolic ring in order for reaction to occur. To further rationalize the molecular basis for reactivity, factors governing substrate recognition were investigated by NMR binding experiments. Additionally, the suitability of substrates for nucleophilic substitution was assessed by molecular modeling using density functional theory (DFT) calculations.
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