Staff Publications

Staff Publications

  • external user (warningwarning)
  • Log in as
  • language uk
  • About

    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

    We have a manual that explains all the features 

Record number 498726
Title Leucanicidin and Endophenasides Result from Methyl-Rhamnosylation by the Same Tailoring Enzymes in Kitasatospora sp. MBT66
Author(s) Wu, C.; Medema, M.H.; Läkamp, R.M.; Zhang, L.; Dorrestein, P.C.; Choi, Y.H.; Wezel, G.P. van
Source Acs Chemical Biology 11 (2016)2. - ISSN 1554-8929 - p. 478 - 490.
DOI http://dx.doi.org/10.1021/acschembio.5b00801
Department(s) Bioinformatics
EPS
Publication type Refereed Article in a scientific journal
Publication year 2016
Abstract The increasing bacterial multidrug resistance necessitates novel drug-discovery efforts. One way to obtain novel chemistry is glycosylation, which is prevalent in nature, with high diversity in both the sugar moieties and the targeted aglycones. Kitasatospora sp. MBT66 produces endophenaside antibiotics, which is a family of (methyl-)rhamnosylated phenazines. Here we show that this strain also produces the plecomacrolide leucanicidin (1), which is derived from bafilomycin A1 by glycosylation with the same methyl-rhamnosyl moiety as present in the endophenasides. Immediately adjacent to the baf genes for bafilomycin biosynthesis lie leuA and leuB, which encode a sugar-O-methyltransferase and a glycosyltransferase, respectively. LeuA and LeuB are the only enzymes encoded by the genome of Kitasatospora sp. MBT66 that are candidates for the methyl-rhamnosylation of natural products, and mutation of leuB abolished glycosylation of both families of natural products. Thus, LeuA and -B mediate the post-PKS methyl-rhamnosylation of bafilomycin A1 to leucanicidin and of phenazines to endophenasides, showing surprising promiscuity by tolerating both macrolide and phenazine skeletons as the substrates. Detailed metabolic analysis by MS/MS based molecular networking facilitated the characterization of nine novel phenazine glycosides 6–8, 16, and 22–26, whereby compounds 23 and 24 represent an unprecedented tautomeric glyceride phenazine, further enriching the structural diversity of endophenasides.
Comments
There are no comments yet. You can post the first one!
Post a comment
 
Please log in to use this service. Login as Wageningen University & Research user or guest user in upper right hand corner of this page.