AvmM catalyses macrocyclization through dehydration/Michael-type addition in alchivemycin A biosynthesis.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 08 2022
03 08 2022
Historique:
received:
08
09
2021
accepted:
15
07
2022
entrez:
3
8
2022
pubmed:
4
8
2022
medline:
6
8
2022
Statut:
epublish
Résumé
Macrocyclization is an important process that affords morphed scaffold in biosynthesis of bioactive natural products. Nature has adapted diverse biosynthetic strategies to form macrocycles. In this work, we report the identification and characterization of a small enzyme AvmM that can catalyze the construction of a 16-membered macrocyclic ring in the biosynthesis of alchivemycin A (1). We show through in vivo gene deletion, in vitro biochemical assay and isotope labelling experiments that AvmM catalyzes tandem dehydration and Michael-type addition to generate the core scaffold of 1. Mechanistic studies by crystallography, DFT calculations and MD simulations of AvmM reveal that the reactions are achieved with assistance from the special tenuazonic acid like moiety of substrate. Our results thus uncover an uncharacterized macrocyclization strategy in natural product biosynthesis.
Identifiants
pubmed: 35922406
doi: 10.1038/s41467-022-32088-4
pii: 10.1038/s41467-022-32088-4
pmc: PMC9349299
doi:
Substances chimiques
Biological Products
0
Macrolides
0
alchivemycin A
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4499Informations de copyright
© 2022. The Author(s).
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