title: The fumagillin biosynthetic gene cluster in Aspergillus fumigatus encodes a cryptic terpene cyclase involved in the formation of β-trans-bergamotene.
abstract: Fumagillin 1 is a meroterpenoid from Aspergillus fumigatus that is known for its anti-angiogenic activity by binding to human methionine aminopeptidase 2. The genetic and molecular basis for biosynthesis of 1 had been an enigma despite the availability of the A. fumigatus genome sequence. Here, we report the identification and verification of the fma gene cluster, followed by characterization of the polyketide synthase and acyltransferase involved in biosynthesis of the dioic acid portion of 1. More significantly, we uncovered the elusive β-trans-bergamotene synthase in A. fumigatus as a membrane-bound terpene cyclase.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California 90095, USA.
authors.forename: Hsiao-Ching
authors.initials: HC
authors.lastname: Lin
authors.forename: Yit-Heng
authors.initials: YH
authors.lastname: Chooi
authors.forename: Sourabh
authors.initials: S
authors.lastname: Dhingra
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Ana M
authors.initials: AM
authors.lastname: Calvo
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
mesh_terms: D001232:Aspergillus fumigatus / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D003510:Cyclohexanes / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000235:genetics* / Q000378:metabolism; D005800:Genes, Fungal; D005810:Multigene Family; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism; D012717:Sesquiterpenes / Q000378:metabolism
chemical_list: D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D012717:Sesquiterpenes; D048630:Polyketide Synthases; C026211:fumagillin