16755-07-0Relevant articles and documents
Showdomycin as a versatile chemical tool for the detection of pathogenesis-associated enzymes in bacteria
Boettcher, Thomas,Sieber, Stephan A.
, p. 6964 - 6972 (2010)
Showdomycin is a potent nucleoside antibiotic that displays a high structural similarity to uridine and pseudouridine. No detailed target analysis of this very unusual electrophilic natural product has been carried out so far. To unravel its biological function, we synthesized a showdomycin probe that can be appended with a fluorophor or a biotin marker via click chemistry and identified diverse enzymes which were important for either the viability or virulence of pathogenic bacteria. Our results indicate that the antibiotic effect of showdomycin against Staphylococcus aureus may be due to the inhibition of various essential enzymes, especially MurA1 and MurA2, which are required for cell wall biosynthesis. Although real-time polymerase chain reaction revealed that the MurA2 gene was expressed equally in four S. aureus strains, our probe studies showed that MurA2 was activated in only one multiresistant S. aureus strain, and only this strain was resistant to elevated concentrations of the MurA inhibitor fosfomycin, suggesting its potential role as an antibiotic bypass mechanism in the case of MurA1 inhibition. Moreover, we utilized this tool to compare enzyme profiles of different pathogenic strains, which provided unique insights in regulatory differences as well as strain-specific signatures.
Identification of a Pyrrole Intermediate Which Undergoes C-Glycosidation and Autoxidation to Yield the Final Product in Showdomycin Biosynthesis
Kim, Minje,Liu, Hung-wen,Ren, Daan,Wang, Shao-An
, p. 17148 - 17154 (2021)
Showdomycin is a C-nucleoside bearing an electrophilic maleimide base. Herein, the biosynthetic pathway of showdomycin is presented. The initial stages of the pathway involve non-ribosomal peptide synthetase (NRPS) mediated assembly of a 2-amino-1H-pyrrole-5-carboxylic acid intermediate. This intermediate is prone to air oxidation whereupon it undergoes oxidative decarboxylation to yield an imine of maleimide, which in turn yields the maleimide upon acidification. It is also shown that this pyrrole intermediate serves as the substrate for the C-glycosidase SdmA in the pathway. After coupling with ribose 5-phosphate, the resulting C-nucleoside undergoes a similar sequence of oxidation, decarboxylation and deamination to afford showdomcyin after exposure to air. These results suggest that showdomycin could be an artifact due to aerobic isolation; however, the autoxidation may also serve to convert an otherwise inert product of the biosynthetic pathway to an electrophilic C-nucleotide thereby endowing showdomycin with its observed bioactivities.
Chirally Selective Synthesis of Sugar Moiety of Nucleosides by Chemicoenzymatic Approach: L- and D-Riboses, Showdomycin, and Cordycepin
Ito, Yukishige,Shibata, Tomoyuki,Arita, Masafumi,Sawai, Hiroaki,Ohno, Masaji
, p. 6739 - 6741 (1981)
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Subclass-specific labeling of protein-reactive natural products with customized nucleophilic probes
Rudolf, Georg C.,Koch, Maximilian F.,Mandl, Franziska A. M.,Sieber, Stephan A.
supporting information, p. 3701 - 3707 (2015/03/04)
Natural products represent a rich source of bioactive compounds that constitute a large fraction of approved drugs. Among those are molecules with electrophilic scaffolds, such as Michael acceptors, b-lactams, and epoxides that irreversibly inhibit essent
A stereocontrolled synthesis of D-(+)-showdomycin
Kang,Lee
, p. 1017 - 1018 (2007/10/02)
Total synthesis of D-(+)-showdomycin 1 is accomplished starting from the enantiomerically pure syn-2,5-disubstituted dihydrofuran 2.
