title: 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.
authors.affiliation: Department of Genetics, University of Wisconsin - Madison, Madison, WI, USA.
authors.forename: Kurt
authors.initials: K
authors.lastname: Throckmorton
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin - Madison, Madison, WI, USA.
authors.forename: Fang Yun
authors.initials: FY
authors.lastname: Lim
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin - Madison, Madison, WI, USA.|Key Laboratory for Biotechnology, Jiangsu Normal University, Xuzhou, China.
authors.forename: Weifa
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin - Madison, Madison, WI, USA.|Department of Bacteriology, University of Wisconsin - Madison, Madison, WI, USA.
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Keller
mesh_terms: D000873:Anthracenes / Q000378:metabolism; D001232:Aspergillus fumigatus / Q000235:genetics / Q000378:metabolism*; D002262:Carboxy-Lyases / Q000235:genetics; D005810:Multigene Family / Q000235:genetics; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D048630:Polyketide Synthases / Q000235:genetics*; D061065:Polyketides / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics; D013172:Spores, Fungal / Q000235:genetics; D000095322:Anthrones
chemical_list: D000873:Anthracenes; D002262:Carboxy-Lyases; D010088:Oxidoreductases; D048630:Polyketide Synthases; D061065:Polyketides; C023523:endocrocin; C004522:anthrone; D000095322:Anthrones