Amycolatopsins A-C: Antimycobacterial Glycosylated Polyketide Macrolides from the Australian Soil Amycolatopsis Sp. MST-108494

Overview

Journal J Antibiot (Tokyo)

Specialties Infectious Diseases
Pharmacology

Date 2017 Oct 26

PMID 29066791

Citations 6

Authors

Zeinab G Khalil

Angela A Salim

Daniel Vuong

Andrew Crombie

Ernest Lacey

Antje Blumenthal

Robert J Capon

Affiliations

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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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