Novel Polyethers from Screening Actinoallomurus spp

Abstract

In screening for novel antibiotics, an attractive element of novelty can be represented by screening previously underexplored groups of microorganisms. We report the results of screening 200 strains belonging to the actinobacterial genus Actinoallomurus for their production of antibacterial compounds. When grown under just one condition, about half of the strains produced an extract that was able to inhibit growth of Staphylococcus aureus. We report here on the metabolites produced by 37 strains. In addition to previously reported aminocoumarins, lantibiotics and aromatic polyketides, we described two novel and structurally unrelated polyethers, designated α-770 and α-823. While we identified only one producer strain of the former polyether, 10 independent Actinoallomurus isolates were found to produce α-823, with the same molecule as main congener. Remarkably, production of α-823 was associated with a common lineage within Actinoallomurus, which includes A.fulvus and A.amamiensis. All polyether producers were isolated from soil samples collected in tropical parts of the world.

Keywords: Actinoallomurus; antibiotics polyethers; screening.

Figure 1

Chemical structures of molecules produced by Actinoallomurus and described in Section 2.2.

Figure 2

Chemical structures of aromatic polyketides produced by Actinoallomurus and described in Section 2.3.

Figure 3

Analysis of α-823. (a) Base peak chromatogram of the 4.0–10.0 min portion with retention times and m/z [M+MH4]⁺ values. Data obtained with a partially purified extract of Actinoallomurus sp. ID145823 (see Table S1 and Figure S7 for the congeners comparison); (b) mass spectrometry (MS) at 8.1 min in positive (above) and negative (below) ionization mode; (c) MS² analysis of m/z [M+NH₄]⁺ 932; (d) putative fragmentation pathway for α-823.

Figure 4

Chemical structure of polyethers produced by Actinoallomurus and described in Section 2.4.

Figure 5

Analysis of α-770. (a) UV chromatogram at 230 nm and UV spectrum of 6.9-min peak. Data obtained with a partially purified extract of Actinoallomurus sp. ID145770; (b) MS at 6.9 min in positive (above) and negative (below) ionization mode; (c) MS² of m/z [M+NH₄]⁺ 852; (d) putative fragmentation pathway for α-770.

Figure 6

Neighbor-joining tree showing the phylogenetic position of polyether-producing Actinoallomurus strains. Type-strains of all described Actinoallomurus species are included. The sequence of the paramagnetoquinone producer Actinoallomurus sp. ID145113 is also included. The tree is based on 1309 unambiguously aligned positions in the 16S rRNA gene sequences. Numbers at the nodes are bootstrap values based on 100 resamplings; only values higher than 60 are shown. Scale bar represents 1 inferred substitutions per 100 nucleotides. The tree was rooted using Streptosporangium roseum 16S rRNA gene sequence (X89947) as outgroup.