Luminmycins A-C，发光杆菌中通过异源表达在大肠杆菌中鉴定出的隐秘天然产物。

Luminmycins A-C, cryptic natural products from Photorhabdus luminescens identified by heterologous expression in Escherichia coli.

机构信息

Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research and Department of Pharmaceutical Biotechnology, Saarland University, P.O. Box 15115, 66041 Saarbrücken, Germany.

出版信息

J Nat Prod. 2012 Sep 28;75(9):1652-5. doi: 10.1021/np300444e. Epub 2012 Aug 21.

DOI:10.1021/np300444e

PMID:22909174

Abstract

The 18 kb "silent" luminmycin biosynthetic pathway from Photorhabdus luminescens was cloned into a vector by using the newly established linear-linear homologous recombination and successfully expressed in Escherichia coli. Luminmycins A-C (1-3) were isolated from the heterologous host, and their structures were elucidated using 2D NMR spectroscopy and HRESIMS. Luminmycin A is a deoxy derivative of the previously reported glidobactin A, while luminmycins B and C most likely represent its acyclic biosynthetic intermediates. Compound 1 showed cytotoxicity against the human colon carcinoma HCT-116 cell line with an IC(50) value of 91.8 nM, while acyclic 2 was inactive at concentrations as high as 100 μg/mL.

摘要

从发光杆菌克隆了 18 kb 的“沉默”亮菌素生物合成途径，通过新建立的线性-线性同源重组将其克隆到载体中，并在大肠杆菌中成功表达。从异源宿主中分离出亮菌素 A-C（1-3），并通过 2D NMR 光谱和 HRESIMS 阐明其结构。亮菌素 A 是先前报道的 glidobactin A 的脱氧衍生物，而亮菌素 B 和 C 很可能代表其无环生物合成中间体。化合物 1 对人结肠癌细胞 HCT-116 系表现出细胞毒性，IC(50)值为 91.8 nM，而无环 2 在高达 100 μg/mL 的浓度下没有活性。