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Re-wiring the regulation of the formicamycin biosynthetic gene cluster to enable the development of promising antibacterial compounds.
Devine, Rebecca; McDonald, Hannah P; Qin, Zhiwei; Arnold, Corinne J; Noble, Katie; Chandra, Govind; Wilkinson, Barrie; Hutchings, Matthew I.
Afiliación
  • Devine R; Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK. Electronic address: rebecca.devine@jic.ac.uk.
  • McDonald HP; Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
  • Qin Z; Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
  • Arnold CJ; Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
  • Noble K; Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
  • Chandra G; Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
  • Wilkinson B; Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK. Electronic address: barrie.wilkinson@jic.ac.uk.
  • Hutchings MI; Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK. Electronic address: matt.hutchings@jic.ac.uk.
Cell Chem Biol ; 28(4): 515-523.e5, 2021 04 15.
Article en En | MEDLINE | ID: mdl-33440167
The formicamycins are promising antibiotics first identified in Streptomyces formicae KY5, which produces the compounds at low levels. Here, we show that by understanding the regulation of the for biosynthetic gene cluster (BGC), we can rewire the BGC to increase production levels. The for BGC consists of 24 genes expressed on nine transcripts. The MarR regulator ForJ represses expression of seven transcripts encoding the major biosynthetic genes as well as the ForGF two-component system that initiates biosynthesis. We show that overexpression of forGF in a ΔforJ background increases formicamycin production 10-fold compared with the wild-type. De-repression, by deleting forJ, also switches on biosynthesis in liquid culture and induces the production of additional, previously unreported formicamycin congeners. Furthermore, combining de-repression with mutations in biosynthetic genes leads to biosynthesis of additional bioactive precursors.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Streptomyces / Staphylococcus aureus Resistente a Meticilina / Antibacterianos Idioma: En Revista: Cell Chem Biol Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Streptomyces / Staphylococcus aureus Resistente a Meticilina / Antibacterianos Idioma: En Revista: Cell Chem Biol Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos