Dataset Information

Redundant synthesis of a conidial polyketide by two distinct secondary metabolite clusters in Aspergillus fumigatus.

ABSTRACT: Filamentous fungi are renowned for the production of bioactive secondary metabolites. Typically, one distinct metabolite is generated from a specific secondary metabolite cluster. Here, we characterize the newly described trypacidin (tpc) cluster in the opportunistic human pathogen Aspergillus fumigatus. We find that this cluster as well as the previously characterized endocrocin (enc) cluster both contribute to the production of the spore metabolite endocrocin. Whereas trypacidin is eliminated when only tpc cluster genes are deleted, endocrocin production is only eliminated when both the tpc and enc non-reducing polyketide synthase-encoding genes, tpcC and encA, respectively, are deleted. EncC, an anthrone oxidase, converts the product released from EncA to endocrocin as a final product. In contrast, endocrocin synthesis by the tpc cluster likely results from incomplete catalysis by TpcK (a putative decarboxylase), as its deletion results in a nearly 10-fold increase in endocrocin production. We suggest endocrocin is likely a shunt product in all related non-reducing polyketide synthase clusters containing homologues of TpcK and TpcL (a putative anthrone oxidase), e.g. geodin and monodictyphenone. This finding represents an unusual example of two physically discrete secondary metabolite clusters generating the same natural product in one fungal species by distinct routes.

SUBMITTER: Throckmorton K

PROVIDER: S-EPMC4750049 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Redundant synthesis of a conidial polyketide by two distinct secondary metabolite clusters in Aspergillus fumigatus.

Throckmorton Kurt K Lim Fang Yun FY Kontoyiannis Dimitrios P DP Zheng Weifa W Keller Nancy P NP

Environmental microbiology 20150903 1

Filamentous fungi are renowned for the production of bioactive secondary metabolites. Typically, one distinct metabolite is generated from a specific secondary metabolite cluster. Here, we characterize the newly described trypacidin (tpc) cluster in the opportunistic human pathogen Aspergillus fumigatus. We find that this cluster as well as the previously characterized endocrocin (enc) cluster both contribute to the production of the spore metabolite endocrocin. Whereas trypacidin is eliminated ...[more]

PMID: 26242966

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Project description:Aerial conidia of Ascomycetes and Basidiomycetes are coated with an amphipathic hydrophobin layer commonly called rodlet layer, that renders their surface hydrophobic and resist wetting, thus facilitating effective dispersal in the air. Fungal hydrophobins are small secreted proteins with specific hydropathy patterns and eight cysteine residues ordered in a particular manner which define the two well characterized classes I and II of hydrophobins and a third intermediate class (Kershaw and Talbot, 1998. Littlejohn et al, 2012; Jensen et al, 2010). Wessels 1994). Class I assemblies are generally water insoluble, have an amyloid structure and form the patterned rodlet layer. Class II are smaller proteins than class I and are soluble in aqueous ethanol mixtures of SDS. The intermediate class is a rather heterogenous tote class which would gather non-class I and non-class II hydrophobins without a defined structure. In addition to the role of the rodlet in the fungal life during conidiogenesis and conidial dispersal in the air, it was shown that rodlets can have a role in fungal – host interactions and favour the pathogenic behavior of the fungal pathogens in humans, plant and insect hosts (Talbot et al., 1996, Aimanianda et al, 2009; Zhang et al, 2011). In Aspergillusfumigatus rodlets immunosilence the conidium and their loss from the conidial surface initiates the host immune response (Aimanianda et al., 2009). Our study is focused on the Rod A protein which forms the rodlet structure on the surface of the conidium of A. fumigatus. In spite of their prominent morphological and biological role, the molecular basis for rodlet self-assembly and desagregation in this fungal species has not been understood yet. Point mutations in the rodA gene have helped understanding the mechanism which drives hydrophobin proteins to assemble into highly ordered structures anchored to the conidium surface. Moreover, the biochemical events responsible for the lysis of the rodlets have been investigated.

Dataset Information

Redundant synthesis of a conidial polyketide by two distinct secondary metabolite clusters in Aspergillus fumigatus.

Publications

Redundant synthesis of a conidial polyketide by two distinct secondary metabolite clusters in Aspergillus fumigatus.

Similar Datasets

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