Luminmycins A-C, Cryptic Natural Products from Photorhabdus luminescens Identified by Heterologous Expression in Escherichia coli

被引:48
作者
Bian, Xiaoying [2 ,3 ]
Plaza, Alberto [2 ,3 ]
Zhang, Youming [1 ]
Mueller, Rolf [2 ,3 ]
机构
[1] Univ Saarland, Gene Bridges GmbH, D-66123 Saarbrucken, Germany
[2] Univ Saarland, Helmholtz Ctr Infect Res, Helmholtz Inst Pharmaceut Res Saarland, D-66123 Saarbrucken, Germany
[3] Univ Saarland, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany
来源
JOURNAL OF NATURAL PRODUCTS | 2012年 / 75卷 / 09期
关键词
CONSTITUENT AMINO-ACIDS; HOMOLOGOUS RECOMBINATION; ABSOLUTE-CONFIGURATION; ANTITUMOR ANTIBIOTICS; MARFEYS METHOD; GLIDOBACTIN-A; CLONING; LC/MS; LOGIC;
D O I
10.1021/np300444e
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
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 IC50 value of 91.8 nM, while acyclic 2 was inactive at concentrations as high as 100 mu g/mL.
引用
收藏
页码:1652 / 1655
页数:4
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