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Heterologous Production of Glidobactins/Luminmycins in Escherichia coli Nissle Containing the Glidobactin Biosynthetic Gene Cluster from Burkholderia DSM7029 |
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| Authors: | Dr. Xiaoying Bian Dr. Fan Huang Dr. Hailong Wang Thorsten Klefisch Prof. Dr. Rolf Müller Prof. Dr. Youming Zhang |
| Affiliation: | 1. Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI) and Department of Pharmaceutical Biotechnology, Saarland University, Campus C2 3, 66123 Saarbrücken, (Germany);2. Shandong University–Helmholtz Joint Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong University, ShandaNanlu 27, 250100 Jinan, (China);3. Department of Genomics, BioInnovationsZentrum, Technische Universit?t Dresden, 01307 Dresden, (Germany) |
| Abstract: | 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. |
| Keywords: | biosynthesis gene expression glidobactin luminmycin natural products promoter exchange |