Please use this identifier to cite or link to this item: http://dx.doi.org/10.14279/depositonce-6088
Main Title: Bacillus subtilis as heterologous host for the secretory production of the non-ribosomal cyclodepsipeptide enniatin
Author(s): Zobel, Sophia
Kumpfmüller, Jana
Süssmuth Roderich D.
Schweder, Thomas
Type: Article
Language Code: en
Abstract: 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.
URI: http://depositonce.tu-berlin.de/handle/11303/6647
http://dx.doi.org/10.14279/depositonce-6088
Issue Date: 2014
Date Available: 28-Aug-2017
DDC Class: 570 Biowissenschaften, Biologie
Subject(s): heterologous expression
Iterative NRPS
cyclodepsipeptide
acoA promoter
acetoin
metabolic engineering
Creative Commons License: https://creativecommons.org/licenses/by/4.0/
Journal Title: Applied microbiology and biotechnology
Publisher: Springer
Publisher Place: Berlin, Heidelberg, New York
Volume: 99
Issue: 2
Publisher DOI: 10.1007/s00253-014-6199-0
Page Start: 681
Page End: 691
EISSN: 1432-0614
ISSN: 0175-7598
Appears in Collections:Technische Universität Berlin » Fakultäten & Zentralinstitute » Fakultät 2 Mathematik und Naturwissenschaften » Institut für Chemie » Fachgebiet Organische Chemie » Publications

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