Heterologous Production of Glidobactins/Luminmycins in Escherichia coli Nissle Containing the Glidobactin Biosynthetic Gene Cluster from Burkholderia DSM7029

被引：40

作者：

Bian, Xiaoying ^{[1
,2
,3
]}

Huang, Fan ^{[4
]}

Wang, Hailong ^{[3
,4
]}

Klefisch, Thorsten ^{[1
,2
]}

Mueller, Rolf ^{[1
,2
]}

Zhang, Youming ^{[3
]}

机构：

[1] Univ Saarland, Helmholtz Inst Pharmaceut Res Saarland HIPS, Helmholtz Ctr Infect Res HZI, Dept Microbial Nat Prod, D-66123 Saarbrucken, Germany

[2] Univ Saarland, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany

[3] Shandong Univ, State Key Lab Microbial Technol, Shandong Univ Helmholtz Joint Inst Biotechnol, Jinan 250100, Peoples R China

[4] Tech Univ Dresden, Dept Genom, BioInnovat Zentrum, D-01307 Dresden, Germany

来源：

CHEMBIOCHEM | 2014年 / 15卷 / 15期

关键词：

biosynthesis; gene expression; glidobactin; luminmycin; natural products; promoter exchange; SYRINGAE PV.-SYRINGAE; POTENT PROTEASOME INHIBITOR; HOMOLOGOUS RECOMBINATION; ANTITUMOR ANTIBIOTICS; CEPAFUNGIN-III; DIRECT CLONING; EXPRESSION; IDENTIFICATION; CHEMISTRY; BIOLOGY;

D O I：

10.1002/cbic.201402199

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Natural product peptide-based proteasome inhibitors show great potential as anticancer drugs. Here we have cloned the biosynthetic gene cluster of a potent proteasome inhibitorglidobactin from Burkholderia DSM7029and successfully detected glidobactins/luminmycins in E. coli Nissle. We have also improved the yield of glidobactin A tenfold by promoter change in a heterologous host. In addition, two new biosynthetic intermediates were identified by comparative MS/MS fragmentation analysis. Identification of acyclic luminmycin E implies substrate specificity of the TE domain for cyclization. The establishment of a heterologous expression system for syrbactins provided the basis for the generation of new syrbactins as proteasome inhibitors by molecular engineering, but the TE domain's specificity cannot be ignored.

引用

页码：2221 / 2224

页数：4