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从聚酮合酶(pks)岛分离出一种代谢物,有助于深入了解大肠杆菌素的生物合成和活性。

Isolation of a metabolite from the pks island provides insights into colibactin biosynthesis and activity.

作者信息

Brotherton Carolyn A, Wilson Matthew, Byrd Gary, Balskus Emily P

机构信息

†Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, United States.

‡Small Molecule Mass Spectrometry Facility, Faculty of Arts and Sciences Division of Science, Harvard University, Cambridge, Massachusetts 02138, United States.

出版信息

Org Lett. 2015 Mar 20;17(6):1545-8. doi: 10.1021/acs.orglett.5b00432. Epub 2015 Mar 10.

Abstract

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.

摘要

大肠杆菌素是一种结构未明确的、具有基因毒性的天然产物,由携带pks岛的共生和致病大肠杆菌菌株产生。一种新的代谢产物已从一个缺失关键生物合成酶的pks(+)大肠杆菌突变体中分离出来。该分子不同寻常的氮杂螺[2.4]双环系统为大肠杆菌素的生物合成提供了新的见解,并提示了一种大肠杆菌素及其他pks衍生代谢产物可能发挥基因毒性的机制。

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