Iron-sulphur protein catalysed [4+2] cycloadditions in natural product biosynthesis.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 Jul 2024
10 Jul 2024
Historique:
received:
29
05
2024
accepted:
02
07
2024
medline:
11
7
2024
pubmed:
11
7
2024
entrez:
10
7
2024
Statut:
epublish
Résumé
To the best of our knowledge, enzymes that catalyse intramolecular Diels-Alder ([4+2] cycloaddition) reactions are frequently reported in natural product biosynthesis; however, no native enzymes utilising Lewis acid catalysis have been reported. Verticilactam is a representative member of polycyclic macrolactams, presumably produced by spontaneous cycloaddition. We report that the intramolecular [4+2] cycloadditions can be significantly accelerated by ferredoxins (Fds), a class of small iron-sulphur (Fe-S) proteins. Through iron atom substitution by Lewis acidic gallium (Ga) iron and computational calculations, we confirm that the ubiquitous Fe-S cluster efficiently functions as Lewis acid to accelerate the tandem [4+2] cycloaddition and Michael addition reactions by lowering free energy barriers. Our work highlights Nature's ingenious strategy to generate complex molecule structures using the ubiquitous Fe-S protein. Furthermore, our study sheds light on the future design of Fd as a versatile Lewis acid catalyst for [4+2] cycloaddition reactions.
Identifiants
pubmed: 38987535
doi: 10.1038/s41467-024-50142-1
pii: 10.1038/s41467-024-50142-1
doi:
Substances chimiques
Biological Products
0
Iron-Sulfur Proteins
0
Lewis Acids
0
Iron
E1UOL152H7
Lactams
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5779Subventions
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 20H00416
Informations de copyright
© 2024. The Author(s).
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