Identification of a Pyrrole Intermediate Which Undergoes C-Glycosidation and Autoxidation to Yield the Final Product in Showdomycin Biosynthesis.
C-glycosidation
C-nucleoside
autoxidation
biosynthesis
maleimide
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
26 07 2021
26 07 2021
Historique:
received:
26
04
2021
pubmed:
29
5
2021
medline:
13
10
2021
entrez:
28
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34048627
doi: 10.1002/anie.202105667
pmc: PMC8292215
mid: NIHMS1710692
doi:
Substances chimiques
Glycosides
0
Pyrroles
0
Showdomycin
E1V8315QHY
Peptide Synthases
EC 6.3.2.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
17148-17154Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM035906
Pays : United States
Organisme : NIGMS NIH HHS
ID : R37 GM035906
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM040541
Pays : United States
Informations de copyright
© 2021 Wiley-VCH GmbH.
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