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| Roles of actinomycete natural products in the leaf-cutter ant ecosystem. Different actinomycete species isolated from attine ant integument (Streptomyces spp., Pseudonocardia spp., etc.) secrete natural products with various functions and roles. (Top left) Streptomyces spp. confer ant immunity by producing valinomycin, antimycins, and actinomycins, which inhibit pathogens and parasites. (Top Right) Actinomycetes produce a range of antifungals including dentigerumycins, candicidin, and nystatin variants, which inhibit fungal pathogens (e.g., Escovopsis spp.) but are not detrimental to the attine ant fungal symbiont, L. gongylophorus. (Bottom Left) Pseudonocardia competing for residency on the ant integument use plasmid-encoded niche defense mechanisms by synthesizing 9-methoxyrebeccamycin. (Bottom Right) Natural products from actinomycetes help preserve the attine ant community, which in turn, affects the larger ecosystem. Leaf-cutter ants forage up to 17% of the foliar biomass and the L. gongylophorus symbiont helps degrade organic material, which collectively contributes to carbon turnover.  

| Roles of actinomycete natural products in the leaf-cutter ant ecosystem. Different actinomycete species isolated from attine ant integument (Streptomyces spp., Pseudonocardia spp., etc.) secrete natural products with various functions and roles. (Top left) Streptomyces spp. confer ant immunity by producing valinomycin, antimycins, and actinomycins, which inhibit pathogens and parasites. (Top Right) Actinomycetes produce a range of antifungals including dentigerumycins, candicidin, and nystatin variants, which inhibit fungal pathogens (e.g., Escovopsis spp.) but are not detrimental to the attine ant fungal symbiont, L. gongylophorus. (Bottom Left) Pseudonocardia competing for residency on the ant integument use plasmid-encoded niche defense mechanisms by synthesizing 9-methoxyrebeccamycin. (Bottom Right) Natural products from actinomycetes help preserve the attine ant community, which in turn, affects the larger ecosystem. Leaf-cutter ants forage up to 17% of the foliar biomass and the L. gongylophorus symbiont helps degrade organic material, which collectively contributes to carbon turnover.  

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Actinomycetes, filamentous actinobacteria found in numerous ecosystems around the globe, produce a wide range of clinically useful natural products (NP). In natural environments, actinomycetes live in dynamic communities where environmental cues and ecological interactions likely influence NP biosynthesis. Our current understating of these cues, an...

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... of the most extensively characterized natural systems that harbor actinomycetes is that of the leaf-cutter ants. Actinobacteria associated with fungus-growing leaf-cutter ants produce NP that have been shown to have key roles in shaping this ecosystem (Figure 1) (Currie et al., 1999). Primarily found in the Americas, leaf-cutter ants (including the genera Atta and Acromyrmex) maintain a delicately balanced network that includes their fungal food source, Leucoagaricus gongylophorus, and actinomycetes, which produce antimicrobials to protect the fungal gardens against pathogen invasion ( Schultz and Brady, 2008;Hölldobler and Wilson, 2010;Andersen et al., 2015). ...
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... antagonism between different species of ant-associated Pseudonocardia was pronounced in more distantly related species, suggesting that competition between Pseudonocardia have shaped this association from its evolutionary origin (Poulsen et al., 2007). Consistent with this idea, Van Arnam et al. (2015) recently found that one Pseudonocardia strain produced a novel rebeccamycin analog that inhibited the growth of competing Pseudonocardia (Figure 1). PacBio sequencing of these strains revealed variations in the rebeccamycin BGCs which were located on plasmids, suggesting plasmid-encoded niche defense (Van Arnam et al., 2015). ...
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... the MALDI-imaging data clearly showed the localization of valinomycin secreted by Streptomyces on the ant cuticle at varying concentrations. Taken together, these data suggest that the presence of integumental biofilms and their secreted NP work in concert to protect fungal gardens from invading bacteria and fungi, while simultaneously contributing to worker ant immunity by inhibiting the growth of entomopathogens (Figure 1) (Schoenian et al., 2011). To corroborate the importance of actinomycete NP in their protective roles against ant-specific pathogens, cuticle-associated biofilms were removed with antibiotic treatment, thereby exposing the ants to attack by the entomopathogenic fungus M. anisopliae, which resulted in increased mortality of Acromyrmex ants ( Mattoso et al., 2012). ...
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... they are the dominant herbivores in much of the Neotropics ( Costa et al., 2008), the foraging activity of leaf- cutter ants has a large impact in the overall function of their ecosystems (Figures 1 and 2). These ants forage up to 17% of the foliar biomass and contribute substantially to carbon turnover in their forest habitats ( Costa et al., 2008). ...

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... They produce more than 70% of bioactive actives with diverse biological activities used in human therapy and other industrially important secondary metabolites [7]. They possess the genetic capacity to produce various kinds of compounds that were never detected in laboratory conditions (Behie et al. 2017). In addition, Streptomyces is one of the most important in the Actinomycetales. ...
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