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Heterologous Production of Glidobactins/Luminmycins in Escherichia coli Nissle Containing the Glidobactin Biosynthetic Gene Cluster from Burkholderia DSM7029
Author(s) -
Bian Xiaoying,
Huang Fan,
Wang Hailong,
Klefisch Thorsten,
Müller Rolf,
Zhang Youming
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201402199
Subject(s) - escherichia coli , heterologous , gene cluster , burkholderia , microbiology and biotechnology , chemistry , heterologous expression , biosynthesis , gene , biology , bacteria , biochemistry , recombinant dna , genetics
Natural product peptide‐based proteasome inhibitors show great potential as anticancer drugs. Here we have cloned the biosynthetic gene cluster of a potent proteasome inhibitor—glidobactin from Burkholderia DSM7029—and 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.