Saccharochelins A-H, Cytotoxic Amphiphilic Siderophores from the Rare Marine Actinomycete Saccharothrix sp. D09.
J Nat Prod
; 84(8): 2149-2156, 2021 08 27.
Article
in En
| MEDLINE
| ID: mdl-34323485
ABSTRACT
Siderophores are secreted by microorganisms to survive in iron-depleted conditions, and they also possess tremendous therapeutic potential. Genomic-inspired isolation facilitated the identification of eight amphiphilic siderophores, saccharochelins A-H (1-8), from a rare marine-derived Saccharothrix species. Saccharochelins feature a series of fatty acyl groups appended to the same tetrapeptide skeleton. With the help of gene disruption and heterologous expression, we identified the saccharochelin biosynthetic pathway. The diversity of saccharochelins originates from the flexible specificity of the starter condensation (CS) domain at the beginning of the nonribosomal peptide synthetase (NRPS) toward various fatty acyl substrates. Saccharochelins showed cytotoxicity against several human tumor cell lines, with IC50 values ranging from 2.3 to 17 µM. Additionally, the fatty acid side chains of the saccharochelins remarkably affected the cytotoxicity, suggesting changing the N-terminal acyl groups of lipopeptides may be a promising approach to produce more potent derivatives.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Actinobacteria
/
Siderophores
Limits:
Humans
Country/Region as subject:
Asia
Language:
En
Journal:
J Nat Prod
Year:
2021
Document type:
Article
Affiliation country:
China