Back to Search Start Over

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

Authors :
Ren D
Kim M
Wang SA
Liu HW
Source :
Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2021 Jul 26; Vol. 60 (31), pp. 17148-17154. Date of Electronic Publication: 2021 Jun 24.
Publication Year :
2021

Abstract

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.<br /> (© 2021 Wiley-VCH GmbH.)

Details

Language :
English
ISSN :
1521-3773
Volume :
60
Issue :
31
Database :
MEDLINE
Journal :
Angewandte Chemie (International ed. in English)
Publication Type :
Academic Journal
Accession number :
34048627
Full Text :
https://doi.org/10.1002/anie.202105667