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EneA of Aspergillus fumigatus is a regulator of secondary metabolism and enhances nscA expression in presence of polyenes and Streptomyces
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EneA of Aspergillus fumigatus is a regulator of secondary metabolism and enhances nscA expression in presence of polyenes and Streptomyces
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Journal Article
EneA of Aspergillus fumigatus is a regulator of secondary metabolism and enhances nscA expression in presence of polyenes and Streptomyces
2026
Overview
Aspergillus fumigatus
is a soil born fungus, which can induce severe aspergillosis in immunocompromised patients. In this study, we investigated the zinc cluster transcription factor EneA (
e
nhancer of
n
scA
e
xpression
A
) of
A. fumigatus
, which is required for adaption to polyenes and for competition with soil living streptomycetes. In presence of polyenes, the polyketidesynthase encoding gene
nscA
, which is part of the neosartoricin/fumicycline gene cluster, is induced in dependency of EneA
via
NscR. In contrast, high levels of
eneA
transcripts lead to increased
nscA
expression in the absence of
nscR
, suggesting differing regulatory pathways for neosartoricin production depending on EneA. Moreover, overexpression of
eneA
leads to the induction of genes from nine different secondary metabolite clusters, comprising several of which are known to produce toxins, revealing EneA as a global regulator of secondary metabolism. We demonstrate that these metabolites reduce amphotericin B toxicity and inhibit the growth of streptomycetes. Finally, we show that polyenes and metabolites derived from
Streptomycetes noursei
promote increased neosartoricin production
via
EneA. These findings suggest that the EneA-dependent adaptation of
A. fumigatus
in its natural habitat may contribute to enhanced tolerance to antifungal agents, such as amphotericin B, and augmented resistance to the host’s immune defenses.
