Heterologous production of glidobactins/luminmycins in Escherichia coli Nissle containing the glidobactin biosynthetic gene cluster from Burkholderia DSM7029.
| Title: | Heterologous production of glidobactins/luminmycins in Escherichia coli Nissle containing the glidobactin biosynthetic gene cluster from Burkholderia DSM7029. |
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| Authors: | Bian X; 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); Shandong University-Helmholtz Joint Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong University, ShandaNanlu 27, 250100 Jinan, (China).; Huang F; Wang H; Klefisch T; Müller R; Zhang Y |
| Source: | Chembiochem : a European journal of chemical biology [Chembiochem] 2014 Oct 13; Vol. 15 (15), pp. 2221-4. Date of Electronic Publication: 2014 Aug 21. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Wiley-VCH Verlag Country of Publication: Germany NLM ID: 100937360 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1439-7633 (Electronic) Linking ISSN: 14394227 NLM ISO Abbreviation: Chembiochem Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Weinheim, Germany : Wiley-VCH Verlag, c2000- |
| MeSH Terms: | Biological Products/*metabolism ; Burkholderia/*genetics ; Escherichia coli/*genetics ; Escherichia coli/*metabolism ; Multigene Family/*genetics ; Oligopeptides/*biosynthesis; Biological Products/chemistry ; Oligopeptides/chemistry ; Oligopeptides/genetics ; Peptides, Cyclic/biosynthesis ; Peptides, Cyclic/chemistry ; Peptides, Cyclic/genetics ; Molecular Conformation ; Stereoisomerism |
| 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.; (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.) |
| Contributed Indexing: | Keywords: biosynthesis; gene expression; glidobactin; luminmycin; natural products; promoter exchange |
| Substance Nomenclature: | 0 (Biological Products); 0 (Oligopeptides); 0 (Peptides, Cyclic); 0 (luminmycin A); 108351-50-4 (glidobactin A) |
| Entry Date(s): | Date Created: 20140823 Date Completed: 20150615 Latest Revision: 20141002 |
| Update Code: | 20260130 |
| DOI: | 10.1002/cbic.201402199 |
| PMID: | 25147087 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't