Elucidation of the relative and absolute stereochemistry of the kalimantacin/batumin antibiotics

Iain Thistlethwaite, Freya Bull, Chengsen Cui, Paul Walker, Shu-Shan Gao, Luoyi Wang, Zhongshu Song, Joleen Masschelein, Rob Lavigne, Matthew Crump, Paul Race, Tom Simpson, Chris Willis

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Abstract

Kalimantacin A and batumin exhibit potent and selective antibiotic activity against Staphylococcus species including MRSA. Both compounds are formed via a hybrid polyketide synthase/non-ribosomal peptide synthetase (PKS-NRPS) biosynthetic pathway and from comparison of the gene clusters it is apparent that batumin from Pseudomonas batumici and kalimantacin from P. fluorescens are the same compound. The linear structure of this unsaturated acid was assigned by spectroscopic methods, but the relative and absolute stereochemistry of the five stereocentres remained unknown. Herein we describe isolation of kalimantacin A and two further metabolites 17,19-diol 2 and 27-descarbamoyl-diol 3 from cultures of P. fluorescens. Their absolute and relative stereochemistries are rigorously determined using a multidisciplinary approach combining natural product degradation and fragment synthesis with bioinformatics and NMR spectroscopy. Diol 2 has the 5R, 15S, 17S, 19R, 26R, 27R configuration and is the immediate biosynthetic precursor of the bioactive kalimantacin A formed by oxidation of the 17-alcohol to the ketone.
Original languageEnglish
Pages (from-to)6196-6201
Number of pages6
JournalChemical Science
Volume8
Issue number9
Early online date11 Jul 2017
DOIs
Publication statusPublished - 1 Sep 2017

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Structured keywords

  • BrisSynBio
  • Bristol BioDesign Institute
  • BCS and TECS CDTs

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