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Saccharochelins A–H, Cytotoxic Amphiphilic Siderophores from the Rare Marine Actinomycete Saccharothrix sp. D09
- Source :
- Journal of Natural Products. 84:2149-2156
- Publication Year :
- 2021
- Publisher :
- American Chemical Society (ACS), 2021.
-
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.
- Subjects :
- Pharmacology
chemistry.chemical_classification
Siderophore
Tetrapeptide
Chemistry
Organic Chemistry
Pharmaceutical Science
Fatty acid
Analytical Chemistry
Complementary and alternative medicine
Biochemistry
Cell culture
Nonribosomal peptide
Drug Discovery
Amphiphile
Molecular Medicine
Heterologous expression
Cytotoxicity
Subjects
Details
- ISSN :
- 15206025 and 01633864
- Volume :
- 84
- Database :
- OpenAIRE
- Journal :
- Journal of Natural Products
- Accession number :
- edsair.doi...........2115760978750879c265dc63296fbbde