Redundant synthesis of a conidial polyketide by two distinct secondary metabolite clusters in Aspergillus fumigatus
2016
Filamentous fungi are renowned for the production of bioactive
secondary metabolites. Typically, one distinct metabolite is generated from a specific
secondary metabolitecluster. 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
anthroneoxidase, 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 synthaseclusters containing homologues of TpcK and TpcL (a putative
anthroneoxidase), e.g. geodin and monodictyphenone. This finding represents an unusual example of two physically discrete
secondary metaboliteclusters generating the same natural product in one fungal species by distinct routes.
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