Bacillus subtilis as heterologous host for the secretory production of the non-ribosomal cyclodepsipeptide enniatin

Verfasser / Beitragende:
[Sophia Zobel, Jana Kumpfmüller, Roderich Süssmuth, Thomas Schweder]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/2(2015-01-01), 681-691
Format:
Artikel (online)
ID: 605505101
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024 7 0 |a 10.1007/s00253-014-6199-0  |2 doi 
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245 0 0 |a Bacillus subtilis as heterologous host for the secretory production of the non-ribosomal cyclodepsipeptide enniatin  |h [Elektronische Daten]  |c [Sophia Zobel, Jana Kumpfmüller, Roderich Süssmuth, Thomas Schweder] 
520 3 |a The heterologous expression of genes or gene clusters in microbial hosts, followed by metabolic engineering of biosynthetic pathways, is key to access industrially and pharmaceutically relevant compounds in an economically affordable and sustainable manner. Therefore, platforms need to be developed, which provide tools for the controlled synthesis of bioactive compounds. The Gram-positive bacterium Bacillus subtilis is a promising candidate for such applications, as it is generally regarded as a safe production host, its physiology is well investigated and a variety of tools is available for its genetic manipulation. Furthermore, this industrially relevant bacterium provides a high secretory potential not only for enzymes but also for primary and secondary metabolites. In this study, we present the first heterologous expression of an eukaryotic non-ribosomal peptide synthetase gene (esyn) coding for the biosynthesis of the small molecule enniatin in B. subtilis. Enniatin is a pharmaceutically used cyclodepsipeptide for treatment of topical bacterial and fungal infections. We generated various enniatin-producing B. subtilis strains, allowing for either single chromosomal or plasmid-based multi-copy expression of the esyn cluster under the control of an acetoin-inducible promoter system. Optimization of cultivation conditions, combined with modifications of the genetic background and multi-copy plasmid-based esyn expression, resulted in a secretory production of enniatin B. This work presents B. subtilis as a suitable host for the expression of heterologous eukaryotic non-ribosomal peptide synthetases (NRPS) clusters. 
540 |a The Author(s), 2014 
690 7 |a Heterologous expression  |2 nationallicence 
690 7 |a Iterative NRPS  |2 nationallicence 
690 7 |a Cyclodepsipeptide  |2 nationallicence 
690 7 |a acoA promoter  |2 nationallicence 
690 7 |a Acetoin  |2 nationallicence 
690 7 |a Metabolic engineering  |2 nationallicence 
700 1 |a Zobel  |D Sophia  |u Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 124, 10623, Berlin, Germany  |4 aut 
700 1 |a Kumpfmüller  |D Jana  |u Institut für Pharmazie, Ernst-Moritz-Arndt-Universität, Felix-Hausdorff-Strasse 3, 17489, Greifswald, Germany  |4 aut 
700 1 |a Süssmuth  |D Roderich  |u Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 124, 10623, Berlin, Germany  |4 aut 
700 1 |a Schweder  |D Thomas  |u Institut für Pharmazie, Ernst-Moritz-Arndt-Universität, Felix-Hausdorff-Strasse 3, 17489, Greifswald, Germany  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/2(2015-01-01), 681-691  |x 0175-7598  |q 99:2<681  |1 2015  |2 99  |o 253 
856 4 0 |u https://doi.org/10.1007/s00253-014-6199-0  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00253-014-6199-0  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zobel  |D Sophia  |u Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 124, 10623, Berlin, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kumpfmüller  |D Jana  |u Institut für Pharmazie, Ernst-Moritz-Arndt-Universität, Felix-Hausdorff-Strasse 3, 17489, Greifswald, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Süssmuth  |D Roderich  |u Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 124, 10623, Berlin, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Schweder  |D Thomas  |u Institut für Pharmazie, Ernst-Moritz-Arndt-Universität, Felix-Hausdorff-Strasse 3, 17489, Greifswald, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/2(2015-01-01), 681-691  |x 0175-7598  |q 99:2<681  |1 2015  |2 99  |o 253