A1 Refereed original research article in a scientific journal

Chemoenzymatic Synthesis of Novel C-Ribosylated Naphthoquinones




AuthorsBastian Blauenburg, Terhi Oja, Karel D Klika, Mikko Metsä-Ketelä

PublisherAMER CHEMICAL SOC

Publishing placeWASHINGTON; 1155 16TH ST, NW, WASHINGTON, DC 20036 USA

Publication year2013

JournalACS Chemical Biology

Journal name in sourceAcs Chemical Biology

Journal acronymACS Chem.Biol.

Number in series11

Volume8

Issue11

First page 2377

Last page2382

Number of pages6

ISSN1554-8929

DOIhttps://doi.org/10.1021/cb400384c(external)


Abstract
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.



Last updated on 2024-26-11 at 13:48