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ORIGINAL RESEARCH article

Front. Chem. Biol.
Sec. Molecular Sciences
Volume 3 - 2024 | doi: 10.3389/fchbi.2024.1445095
This article is part of the Research Topic Biosynthesis of secondary metabolites in bacteria: genes, pathways, and evolution View all 4 articles

Generation of lysolipin derivatives by genetic engineering

Provisionally accepted
Helene Robertsen Helene Robertsen 1Sabrina Rohrer Sabrina Rohrer 1Andreas Kulik Andreas Kulik 1Wolfgang Wohlleben Wolfgang Wohlleben 1*Yvonne Mast Yvonne Mast 2*
  • 1 Department of Microbiology/Biotechnology, University of Tübingen, Tübingen, Baden-Württemberg, Germany
  • 2 Department Bioresources for Bioeconomy and Health Research, German Collection of Microorganisms and Cell Cultures GmbH (DSMZ), Braunschweig, Germany

The final, formatted version of the article will be published soon.

    Lysolipin I is a halogenated, polycyclic xanthone natural product belonging to the polyketide class of antibiotics, naturally produced by Streptomyces violaceoniger TÜ96 and Streptomyces tendae TÜ4042. The biosynthesis is encoded on a 43 kb-spanning biosynthetic gene cluster. Heterologous expression of the gene cluster has been established in previous work by using the cosmid 4H04, which was transferred to Streptomyces albus. In the current study, we demonstrate the optimization of production yields of therapeutically interesting lysolipin derivatives with extended activity against Gram-negatives and less cytotoxic bioactivities, respectively, by using mutated heterologous S. albus producer strains. Production yields were significantly increased by adapting cultivation conditions as well as by inactivating the transcriptional repressor gene llpRI, which lead to increased and consistent lysolipin (derivatives) production. Furthermore, cultivation of a S. albus 4H04∆llpOI mutant strain in bromide-containing fermentation medium resulted in the production of a new brominated lysolipin derivative (C28H20BrNO9).

    Keywords: Actinomycetes, Streptomyces, antibiotic, Polyketides, lysolipin, Genetic Engineering

    Received: 06 Jun 2024; Accepted: 16 Jul 2024.

    Copyright: © 2024 Robertsen, Rohrer, Kulik, Wohlleben and Mast. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Wolfgang Wohlleben, Department of Microbiology/Biotechnology, University of Tübingen, Tübingen, 72074, Baden-Württemberg, Germany
    Yvonne Mast, Department Bioresources for Bioeconomy and Health Research, German Collection of Microorganisms and Cell Cultures GmbH (DSMZ), Braunschweig, Germany

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