Issue 9, 2017

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

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-descarbomyl hydroxyketone 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.

Graphical abstract: Elucidation of the relative and absolute stereochemistry of the kalimantacin/batumin antibiotics

Supplementary files

Article information

Article type
Edge Article
Submitted
14 Apr 2017
Accepted
02 Jul 2017
First published
11 Jul 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2017,8, 6196-6201

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

I. R. G. Thistlethwaite, Freya M. Bull, C. Cui, P. D. Walker, S. Gao, L. Wang, Z. Song, J. Masschelein, R. Lavigne, M. P. Crump, P. R. Race, T. J. Simpson and C. L. Willis, Chem. Sci., 2017, 8, 6196 DOI: 10.1039/C7SC01670K

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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