Novel expression hosts for complex secondary metabolite megasynthetases: Production of myxochromide in the thermopilic isolate Corallococcus macrosporus GT-2

doi:10.1186/1475-2859-8-1

Microbial Cell Factories

Volume 8

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Perlova O
Gerth K
Kuhlmann S
Zhang Y
Müller R

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Müller R
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Novel expression hosts for complex secondary metabolite megasynthetases: Production of myxochromide in the thermopilic isolate Corallococcus macrosporus GT-2

Olena Perlova¹^* , Klaus Gerth²^* , Silvia Kuhlmann¹ , Youming Zhang³ and Rolf Müller¹^,2

¹Institut für Pharmazeutische Biotechnologie, Universität des Saarlandes, Postfach 15 11 50, D-66041 Saarbrücken, Germany

²Helmholtz-Zentrum für Infektionsforschung GmbH, MWIS, Inhoffenstraße 7, D-38124 Braunschweig, Germany

³Gene Bridges GmbH, BioInnovationsZentrum, Tatzberg 47, 01307 Dresden, Germany

author email corresponding author email* Contributed equally

Microbial Cell Factories 2009, 8:1doi:10.1186/1475-2859-8-1


Published:	6 January 2009

Abstract

Although many secondary metabolites with diverse biological activities have been isolated from myxobacteria, most strains of these biotechnologically important gliding prokaryotes remain difficult to handle genetically. In this study we describe the new fast growing myxobacterial thermophilic isolate GT-2 as a heterologous host for the expression of natural product biosynthetic pathways isolated from other myxobacteria. According to the results of sequence analysis of the 16S rDNA, this moderately thermophilic isolate is closely related to Corallococcus macrosporus and was therefore named C. macrosporus GT-2. Fast growth of moderately thermophilic strains results in shorter fermentation and generation times, aspects which are of significant interest for molecular biological work as well as production of secondary metabolites. Development of a genetic manipulation system allowed the introduction of the complete myxochromide biosynthetic gene cluster, located on a transposable fragment, into the chromosome of GT-2. Genetic engineering of the biosynthetic gene cluster by promoter exchange leads to much higher production of myxochromides in the heterologous host C. macrosporus GT-2 in comparison to the original producer Stigmatella aurantiaca and to the previously described heterologous host Pseudomonas putida (600 mg/L versus 8 mg/L and 40 mg/L, respectively).