NDLI: Identification of the antiphagocytic trypacidin gene cluster in the human-pathogenic fungus Aspergillus fumigatus

Content Provider	Springer Nature Link
Author	Mattern, Derek J. Schoeler, Han Weber, Jakob vohradská, Silvia Kraibooj, Kaswara Dahse, Hans Martin Hillmann, Falk Valiante, Vito Figge, Marc Thilo Brakhage, Axel A.
Copyright Year	2015
Abstract	The opportunistic human pathogen Aspergillus fumigatus produces numerous different natural products. The genetic basis for the biosynthesis of a number of known metabolites has remained unknown. The gene cluster encoding for the biosynthesis of the conidia-bound metabolite trypacidin is of particular interest because of its antiprotozoal activity and possible role in the infection process. Here, we show that the genes encoding the biosynthesis enzymes of trypacidin reside within an orphan gene cluster in A. fumigatus. Genome mining identified tynC as an uncharacterized polyketide synthase with high similarity to known enzymes, whose products are structurally related to trypacidin including endocrocin and fumicycline. Gene deletion of tynC resulted in the complete absence of trypacidin production, which was fully restored when the mutant strain was complemented with the wild-type gene. When confronted with macrophages, the tynC deletion mutant conidia were more frequently phagocytosed than those of the parental wild-type strain. This was also found for phagocytic amoebae of the species Dictyostelium discoideum, which showed increased phagocytosis of ΔtynC conidia. Both macrophages and amoebae were also sensitive to trypacidin. Therefore, our results suggest that the conidium-bound trypacidin could have a protective function against phagocytes both in the environment and during the infection process.
Starting Page	10151
Ending Page	10161
Page Count	11
File Format	PDF
ISSN	01757598
Journal	Applied Microbiology and Biotechnology
Volume Number	99
Issue Number	23
e-ISSN	14320614
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2015-08-18
Publisher Place	Berlin, Heidelberg
Access Restriction	Subscribed
Subject Keyword	Aspergillus fumigatus Genome mining Trypacidin Polyketide Macrophage Dictyostelium discoideum Microbiology Microbial Genetics and Genomics Biotechnology
Content Type	Text
Resource Type	Article
Subject	Medicine Applied Microbiology and Biotechnology Biotechnology

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