Isolation of a Metabolite from the pks Island Provides Insights into Colibactin Biosynthesis and Activity

被引:56
作者
Brotherton, Carolyn A. [1 ]
Wilson, Matthew [1 ]
Byrd, Gary [2 ]
Balskus, Emily P. [1 ]
机构
[1] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA
[2] Harvard Univ, Small Mol Mass Spectrometry Facil, Fac Arts & Sci, Div Sci, Cambridge, MA 02138 USA
关键词
IN-VIVO; DNA; DERIVATIVES; ACTIVATION; CHEMISTRY; MECHANISM; CC-1065;
D O I
10.1021/acs.orglett.5b00432
中图分类号
O62 [有机化学];
学科分类号
070303 [有机化学];
摘要
Colibactin is a structurally uncharacterized, genotoxic natural product produced by commensal and pathogenic strains of E. coli that harbor the pks island. A new metabolite has been isolated from a pks(+) E. coli mutant missing an essential biosynthetic enzyme. The unusual azaspiro[2.4] bicyclic ring system of this molecule provides new insights into colibactin biosynthesis and suggests a mechanism through which colibactin and other pks-derived metabolites may exert genotoxicity.
引用
收藏
页码:1545 / 1548
页数:4
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