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Bacterial type III polyketide synthases: phylogenetic analysis and potential for the production of novel secondary metabolites by heterologous expression in pseudomonads

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Abstract

Type III polyketide synthases (PKS) were regarded as typical for plant secondary metabolism before they were found in microorganisms recently. Due to microbial genome sequencing efforts, more and more type III PKS are found, most of which of unknown function. In this manuscript, we report a comprehensive analysis of the phylogeny of bacterial type III PKS and report the expression of a type III PKS from the myxobacterium Sorangium cellulosum in pseudomonads. There is no precedent of a secondary metabolite that might be biosynthetically correlated to a type III PKS from any myxobacterium. Additionally, an inactivation mutant of the S. cellulosum gene shows no physiological difference compared to the wild-type strain which is why these type III PKS are assumed to be “silent” under the laboratory conditions administered. One type III PKS (SoceCHS1) was expressed in different Pseudomonas sp. after the heterologous expression in Escherichia coli failed. Cultures of recombinant Pseudomonas sp. harbouring SoceCHS1 turned red upon incubation and the diffusible pigment formed was identified as 2,5,7-trihydroxy-1,4-naphthoquinone, the autooxidation product of 1,3,6,8-tetrahydroxynaphthalene. The successful heterologous production of a secondary metabolite using a gene not expressed under administered laboratory conditions provides evidence for the usefulness of our approach to activate such secondary metabolite genes for the production of novel metabolites.

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Acknowledgments

Authentic flaviolin reference substance was a kind gift from Prof. Dr. H. Anke, Kaiserlautern. The authors highly appreciate the help of D. Krug and P. Meiser in the chemical analysis of flaviolin. This work was supported by the German Ministry for Education and Research (BMB+F, BioFuture program) and the Deutsche Forschungsgemeinschaft (DFG) within the Schwerpunktprogramm “evolution of metabolic diversity”.

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Author notes

  1. Frank Gross

    Present address: Gene Bridges GmbH, Tatzberg 47-51, 01307, Dresden, Germany

  2. Nikolaos Gaitatzis

    Present address: Biotica Technology Ltd., Chesterford Research Park, Little Chesterford,, CB10 1XL, Nr Saffron Walden, Essex, UK

Authors and Affiliations

  1. Institut für Pharmazeutische Biotechnologie, Universität des Saarlandes, Postfach 151150, 66041, Saarbrücken, Germany

    Frank Gross, Nora Luniak, Olena Perlova, Nikolaos Gaitatzis & Rolf Müller

  2. Institut für Pharmazeutische Biologie, Technische Universität Carolo-Wilhelmina, Mendelsohnstr. 1, 38106, Braunschweig, Germany

    Frank Gross, Daniela Gottschalk & Rolf Müller

  3. Gesellschaft für Biotechnologische Forschung mbH, Mascheroder Weg 1, 38124, Braunschweig, Germany

    Frank Gross, Klaus Gerth, Daniela Gottschalk & Rolf Müller

  4. Institut für Biologie, Humboldt Universität, Chausseestr. 117, Berlin, Germany

    Holger Jenke-Kodama & Elke Dittmann

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  1. Frank Gross
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Correspondence to Rolf Müller.

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Frank Gross and Nora Luniak contributed equally to this work

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Gross, F., Luniak, N., Perlova, O. et al. Bacterial type III polyketide synthases: phylogenetic analysis and potential for the production of novel secondary metabolites by heterologous expression in pseudomonads. Arch Microbiol 185, 28–38 (2006). https://doi.org/10.1007/s00203-005-0059-3

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