Uncovering the chemistry of C–C bond formation inC-nucleoside biosynthesis: crystal structure of aC-glycoside synthase/PRPP complex

Abstract

<p>X-Ray crystal structure of a novel <italic>C</italic>-glycoside synthase involved in the biosynthesis of biologically active <italic>C</italic>-nucleosides and <italic>C</italic>-nucleotides.</p>

Reverse C-glycosidase reaction provides C-nucleotide building blocks of xenobiotic nucleic acids

“…Other C-nucleosides, such as showdomycin, formycin, pseudouridimycin and minimycin ( Supplementary Fig. 1), constitute an emerging class of microbial natural products that exhibit unusual structures and diverse biological activities, including antibiotic efficacy [15][16][17][18][19][20][21] .…”

“…A synthesis that exploits the high stereo-and regiocontrol of enzymatic reactions for installing the C-glycosidic linkage would be highly desirable. Natural enzymes of C-glycoside biosynthesis, such as tRNA pseudouridine synthase 27,28,51,52 and C-glycosynthase 15,[18][19][20][21]53,54 have complex substrate requirements, leading to perceived limitations on their applicability. Therefore, unlike N-nucleosides for which N-nucleoside phosphorylases present excellent tools of glycoside synthesis [55][56][57][58][59][60] , biocatalytic methods are lacking for C-nucleoside synthetic chemistry.…”

Biocatalytic routes to anti-viral agents and their synthetic intermediates

“…Currently, adequate biocatalytic methods for installing the chiral quaternary centre are lacking. Novel C-C bond forming enzymes are required to catalyse the desired transformation, since neither the enzymes involved in the biosynthesis of C-nucleosides, 406 nor known oxynitrilases match the requirements. 407…”

Identification of a Pyrrole Intermediate Which Undergoes C‐Glycosidation and Autoxidation to Yield the Final Product in Showdomycin Biosynthesis

“…[14][15][16] Both utilize phosphoribosyl pyrophosphate (PRPP) as the ribose donor, and the reactions proceed via electrophilic aromatic substitution. [14,16] In contrast to ForT and PyfQ,h owever,e arly studies of pseudouridine (4)biosynthesis showed that pseudouridine monophosphate synthase (YeiN) catalyzes C-glycosidic bond formation and cleavage between ribose 5-phosphate (14,R 5P) and uracil through ar ibose ring-opening mechanism. [17,18] Likewise,A lnA in alnumycin C1 (5)b iosynthesis exhibits moderate homology to YeiN and appears to catalyze the attachment of R5P to the polyketide aglycone via am echanism involving an enediolate intermediate.…”