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Formicamycin biosynthesis involves a unique reductive ring contraction.
Qin, Zhiwei; Devine, Rebecca; Booth, Thomas J; Farrar, Elliot H E; Grayson, Matthew N; Hutchings, Matthew I; Wilkinson, Barrie.
Afiliación
  • Qin Z; Department of Molecular Microbiology , John Innes Centre , Norwich Research Park , Norwich , NR4 7UH , UK . Email: barrie.wilkinson@jic.ac.uk.
  • Devine R; School of Biological Sciences , University of East Anglia , Norwich Research Park , Norwich , NR4 7TJ , UK . Email: matt.hutchings@jic.ac.uk.
  • Booth TJ; Department of Molecular Microbiology , John Innes Centre , Norwich Research Park , Norwich , NR4 7UH , UK . Email: barrie.wilkinson@jic.ac.uk.
  • Farrar EHE; Department of Chemistry , University of Bath , Claverton Down , Bath BA2 7AY , UK.
  • Grayson MN; Department of Chemistry , University of Bath , Claverton Down , Bath BA2 7AY , UK.
  • Hutchings MI; Department of Molecular Microbiology , John Innes Centre , Norwich Research Park , Norwich , NR4 7UH , UK . Email: barrie.wilkinson@jic.ac.uk.
  • Wilkinson B; School of Biological Sciences , University of East Anglia , Norwich Research Park , Norwich , NR4 7TJ , UK . Email: matt.hutchings@jic.ac.uk.
Chem Sci ; 11(31): 8125-8131, 2020 Aug 21.
Article en En | MEDLINE | ID: mdl-33033611
Fasamycin natural products are biosynthetic precursors of the formicamycins. Both groups of compounds are polyketide natural products that exhibit potent antibacterial activity despite displaying different three-dimensional topologies. We show here that transformation of fasamycin into formicamycin metabolites requires two gene products and occurs via a novel two-step ring expansion-ring contraction pathway. Deletion of forX, encoding a flavin dependent monooxygenase, abolished formicamycin production and leads to accumulation of fasamycin E. Deletion of the adjacent gene forY, encoding a flavin dependent oxidoreductase, also abolished formicamycin biosynthesis and led to the accumulation of new lactone metabolites that represent Baeyer-Villiger oxidation products of the fasamycins. These results identify ForX as a Baeyer-Villiger monooxygenase capable of dearomatizing ring C of the fasamycins. Through in vivo cross feeding and biomimetic semi-synthesis experiments we showed that these lactone products represent biosynthetic intermediates that are reduced to formicamycins in a unique reductive ring contraction reaction catalyzed by ForY.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Chem Sci Año: 2020 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Chem Sci Año: 2020 Tipo del documento: Article Pais de publicación: Reino Unido