Non-modular fatty acid synthases yield distinct N-terminal acylation in ribosomal peptides.
Nat Chem
; 16(8): 1320-1329, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38528101
ABSTRACT
Recent efforts in genome mining of ribosomally synthesized and post-translationally modified peptides (RiPPs) have expanded the diversity of post-translational modification chemistries. However, RiPPs are rarely reported as hybrid molecules incorporating biosynthetic machinery from other natural product families. Here we report lipoavitides, a class of RiPP/fatty-acid hybrid lipopeptides that display a unique, putatively membrane-targeting 4-hydroxy-2,4-dimethylpentanoyl (HMP)-modified N terminus. The HMP is formed via condensation of isobutyryl-coenzyme A (isobutyryl-CoA) and methylmalonyl-CoA catalysed by a 3-ketoacyl-(acyl carrier protein) synthase III enzyme, followed by successive tailoring reactions in the fatty acid biosynthetic pathway. The HMP and RiPP substructures are then connected by an acyltransferase exhibiting promiscuous activity towards the fatty acyl and RiPP substrates. Overall, the discovery of lipoavitides contributes a prototype of RiPP/fatty-acid hybrids and provides possible enzymatic tools for lipopeptide bioengineering.
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Base de datos:
MEDLINE
Asunto principal:
Ribosomas
Idioma:
En
Revista:
Nat Chem
Asunto de la revista:
QUIMICA
Año:
2024
Tipo del documento:
Article