Amycolatopsins A-C: antimycobacterial glycosylated polyketide macrolides from the Australian soil Amycolatopsis sp. MST-108494

  • J Antibiot (Tokyo). 2017 Dec;70(12):1097-1103. doi: 10.1038/ja.2017.119.
Zeinab G Khalil  1  2 ,  Angela A Salim  1 ,  Daniel Vuong  3 ,  Andrew Crombie  3 ,  Ernest Lacey  3 ,  Antje Blumenthal  2 ,  Robert J Capon  1
Affiliations
  • 1. Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia.
  • 2. The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD, Australia.
  • 3. Microbial Screening Technologies, Smithfield, NSW, Australia.
PMID: 29066791 DOI: 10.1038/ja.2017.119
Abstract

A southern Australian soil isolate, Amycolatopsis sp. MST-108494, was subjected to a panel of fermentation and media optimization trials, supported by analytical chemical profiling, to detect and enhance production of a rare class of secondary metabolites. Chemical fractionation of two complementary fermentations yielded three new polyketides, identified by detailed spectroscopic analysis as the glycosylated macrolactones, amycolatopsins A (1), B (2) and C (3), closely related to the ammocidins and apoptolidins. Amycolatopsins 1 and 3 selectively inhibited growth of Mycobacterium bovis (BCG) and Mycobacterium tuberculosis (H37Rv) when compared with Other Gram-positive or Gram-negative bacteria, with 3 exhibiting low levels of cytotoxicity toward mammalian cells. Thus, our data reveal promising structure activity relationship correlations where the antimycobacterial properties of amycolatopsins are enhanced by hydroxylation of the 6-Me (that is, 1 and 3), whereas mammalian cytotoxicity is decreased by hydrolysis of the disaccharide moiety (that is, 3).

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