Skip to content

Selected Mutations Reveal New Intermediates in the Biosynthesis of Mupirocin and the Thiomarinol Antibiotics

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)3930-3934
Number of pages5
JournalAngewandte Chemie - International Edition
Volume56
Issue number14
Early online date9 Feb 2017
DOIs
DateAccepted/In press - 20 Jan 2017
DateE-pub ahead of print - 9 Feb 2017
DatePublished (current) - 27 Mar 2017

Abstract

Thiomarinol and mupirocin are assembled on similar polyketide/fatty acid backbones and exhibit potent antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA). They both contain a tetrasubstituted tetrahydropyran (THP) ring that is essential for biological activity. Mupirocin is a mixture of pseudomonic acids (PAs). Isolation of the novel compound mupirocin P, which contains a 7-hydroxy-6-keto-substituted THP, from a ΔmupP strain and chemical complementation experiments confirm that the first step in the conversion of PA-B into the major product PA-A is oxidation at the C6 position. In addition, nine novel thiomarinol (TM) derivatives with different oxidation patterns decorating the central THP core were isolated after gene deletion (tmlF). These metabolites are in accord with the THP ring formation and elaboration in thiomarinol following a similar order to that found in mupirocin biosynthesis, despite the lack of some of the equivalent genes. Novel mupirocin–thiomarinol hybrids were also synthesized by mutasynthesis.

    Structured keywords

  • BioDesign
  • BrisSynBio

    Research areas

  • Antibiotics, Biosynthesis, Mutasynthesis, Polyketides, Structure determination, synthetic biology

Download statistics

No data available

Documents

Documents

  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Wiley at http://onlinelibrary.wiley.com/doi/10.1002/anie.201611590/abstract . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 689 KB, PDF-document

DOI

View research connections

Related faculties, schools or groups