Genome-Led Discovery of the Antibacterial Cyclic Lipopeptide Kutzneridine A and Its Silent Biosynthetic Gene Cluster from Kutzneria Species

被引:1
|
作者
Ortiz-Lopez, Francisco Javier [1 ]
Oves-Costales, Daniel [1 ]
Garzon, Jaime Felipe Guerrero [2 ]
Gren, Tetiana [2 ]
Sterndorff, Eva Baggesgaard [2 ]
Jiang, Xinglin [2 ]
Jorgensen, Tue Sparholt [2 ]
Blin, Kai [2 ]
Fernandez-Pastor, Ignacio [1 ]
Tormo, Jose R. [1 ]
Martin, Jesus [1 ]
Sanchez, Pilar [1 ]
Moreno, Mercedes de la Cruz [1 ]
Reyes, Fernando [1 ]
Genilloud, Olga [1 ]
Weber, Tilmann [2 ]
机构
[1] Fdn MEDINA, Ctr Excelencia Invest Medicamentos Innovadores And, Granada 18016, Spain
[2] Tech Univ Denmark, Novo Nordisk Fdn, Ctr Biosustainabil, DK-2800 Lyngby, Denmark
来源
JOURNAL OF NATURAL PRODUCTS | 2024年 / 87卷 / 10期
关键词
NATURAL-PRODUCTS; PEPTIDE; CHONBURIENSIS; ANTIBIOTICS; MECHANISM;
D O I
10.1021/acs.jnatprod.4c00633
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Genome analysis of Kutzneria sp. CA-103260 revealed a putative lipopeptide-encoding biosynthetic gene cluster (BGC) that was cloned into a bacterial artificial chromosome (BAC) and heterologously expressed in Streptomyces coelicolor M1152. As a result, a novel cyclic lipo-tetrapeptide containing two diaminopropionic acid residues and an exotic N,N-acetonide ring, kutzneridine A (1), was isolated and structurally characterized. Evaluation of the extraction conditions and isotope-labeling chemical modifications showed that the acetonide ring originated from acetone during isolation. The BGC was analyzed in silico and a biosynthetic pathway to 1 was proposed. Kutzneridine A displayed remarkable antibacterial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci.
引用
收藏
页码:2515 / 2522
页数:8
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