title: Genome-based cluster deletion reveals an endocrocin biosynthetic pathway in Aspergillus fumigatus.
abstract: Endocrocin is a simple anthraquinone frequently identified in extracts of numerous fungi. Several biosynthetic schemes for endocrocin synthesis have been hypothesized, but to date, no dedicated secondary metabolite gene cluster that produces this polyketide as its major metabolite has been identified. Here we describe our biosynthetic and regulatory characterization of the endocrocin gene cluster in Aspergillus fumigatus. This is the first report of this anthraquinone in this species. The biosynthetic genes required for endocrocin production are regulated by the global regulator of secondary metabolism, LaeA, and encode an iterative nonreducing polyketide synthase (encA), a physically discrete metallo-β-lactamase type thioesterase (encB), and a monooxygenase (encC). Interestingly, the deletion of a gene immediately adjacent to encC, termed encD and encoding a putative 2-oxoglutarate-Fe(II) type oxidoreductase, resulted in higher levels of endocrocin production than in the wild-type strain, whereas overexpression of encD eliminated endocrocin accumulation. We found that overexpression of the encA transcript resulted in higher transcript levels of encA-D and higher production of endocrocin. We discuss a model of the enc cluster as one evolutionary origin of fungal anthraquinones derived from a nonreducing polyketide synthase and a discrete metallo-β-lactamase-type thioesterase.
authors.affiliation: Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Fang Yun
authors.initials: FY
authors.lastname: Lim
authors.forename: Yanpeng
authors.initials: Y
authors.lastname: Hou
authors.forename: Yiming
authors.initials: Y
authors.lastname: Chen
authors.forename: Jee-Hwan
authors.initials: JH
authors.lastname: Oh
authors.forename: Inhyung
authors.initials: I
authors.lastname: Lee
authors.forename: Tim S
authors.initials: TS
authors.lastname: Bugni
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Keller
mesh_terms: D000873:Anthracenes / Q000378:metabolism; D001232:Aspergillus fumigatus / Q000235:genetics* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics; D053898:Biosynthetic Pathways / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D005810:Multigene Family; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics
chemical_list: D000873:Anthracenes; D001426:Bacterial Proteins; D014157:Transcription Factors; C023523:endocrocin