Journal article

Biosynthesis and Ether-Bridge Formation in Nargenicin Macrolides

Sacha J Pidot, Marion Herisse, Liam Sharkey, Liselle Atkin, Jessica L Porter, Torsten Seemann, Benjamin P Howden, Mark A Rizzacasa, Timothy P Stinear

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | WILEY-V C H VERLAG GMBH | Published : 2019

Abstract

The nargenicin family of antibiotics are macrolides containing a rare ether-bridged cis-decalin motif. Several of these compounds are highly active against multi-drug resistant organisms. Despite the identification of the first members of this family almost 40 years ago, the genetic basis for the production of these molecules and the enzyme responsible for formation of the oxa bridge, remain unknown. Here, the 85 kb nargenicin biosynthetic gene cluster was identified from a human pathogenic Nocardia arthritidis isolate and this locus is solely responsible for nargenicin production. Further investigation of this locus revealed a putative iron-α-ketoglutarate-dependent dioxygenase, which was f..

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Grants

Awarded by Australian National Health and Medical Research Council


Funding Acknowledgements

We wish to thank Ching-Seng Ang, Shuai Nai, and Nick Williamson at the Bio21 Mass Spectrometry and Proteomics Facility for helpful discussions and assistance with mass spectrometry. This work was supported by an Australian National Health and Medical Research Council grant GNT1105522.