Digitoxosyltetracenomycin C and glucosyltetracenomycin C, two novel elloramycin analogues obtained by exploring the sugar donor substrate specificity of glycosyltransferase ElmGT.
Our explorations of glycosyltransferase ElmGT from Streptomyces olivaceus Tü 2353, which shows an interesting flexibility regarding its sugar donor substrate, were extended toward various previously unexplored sugar co-substrates. The studies revealed that ElmGT, which normally transfers L-rhamnose to 8-demethyltetracenomycin C as a crucial biosynthetic step in elloramycin biosynthesis, is also able to process an activated non-deoxygenated sugar, NDP-D-glucose, as well as NDP-L-digitoxose, which is the first example of an NDP-L-sugar co-substrate of ElmGT possessing an axial 3-OH group. The structures of the resulting novel elloramycin analogues of these experiments, 8-demethyl-8-L-digitoxosyltetracenomycin C (4) and 8-demethyl-8-D-glucosyltetracenomycin C (7), were elucidated mainly by (1)H and (13)C NMR spectroscopy and by mass spectrometry.
Fischer
Carsten
C
Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536, USA.
Rodríguez
Leticia
L
Patallo
Eugenio P
EP
Lipata
Fredilyn
F
Braña
Alfredo F
AF
Méndez
Carmen
C
Salas
Jose A
JA
Rohr
Jürgen
J
D000880:Anthraquinones / Q000737:chemistry* / Q000302:isolation & purification* / Q000378:metabolism* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000378:metabolism; D002384:Catalysis; D016695:Glycosyltransferases / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D010957:Plasmids / Q000378:metabolism; D013302:Streptomyces / Q000201:enzymology*; D013379:Substrate Specificity
D000880:Anthraquinones; D000900:Anti-Bacterial Agents; C471817:digitoxosyltetracenomycin C; C471816:glucosyltetracenomycin C; C047329:elloramycin; D016695:Glycosyltransferases