O-methyltransferase-like enzyme catalyzed diazo installation in polyketide biosynthesis.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
04 09 2023
04 09 2023
Historique:
received:
20
12
2022
accepted:
17
08
2023
medline:
6
9
2023
pubmed:
5
9
2023
entrez:
4
9
2023
Statut:
epublish
Résumé
Diazo compounds are rare natural products possessing various biological activities. Kinamycin and lomaiviticin, two diazo natural products featured by the diazobenzofluorene core, exhibit exceptional potency as chemotherapeutic agents. Despite the extensive studies on their biosynthetic gene clusters and the assembly of their polyketide scaffolds, the formation of the characteristic diazo group remains elusive. L-Glutamylhydrazine was recently shown to be the hydrazine donor in kinamycin biosynthesis, however, the mechanism for the installation of the hydrazine group onto the kinamycin scaffold is still unclear. Here we describe an O-methyltransferase-like protein, AlpH, which is responsible for the hydrazine incorporation in kinamycin biosynthesis. AlpH catalyses a unique SAM-independent coupling of L-glutamylhydrazine and polyketide intermediate via a rare Mannich reaction in polyketide biosynthesis. Our discovery expands the catalytic diversity of O-methyltransferase-like enzymes and lays a strong foundation for the discovery and development of novel diazo natural products through genome mining and synthetic biology.
Identifiants
pubmed: 37666836
doi: 10.1038/s41467-023-41062-7
pii: 10.1038/s41467-023-41062-7
pmc: PMC10477347
doi:
Substances chimiques
Methyltransferases
EC 2.1.1.-
Biological Products
0
Polyketides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5372Informations de copyright
© 2023. Springer Nature Limited.
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