title: Two separate gene clusters encode the biosynthetic pathway for the meroterpenoids austinol and dehydroaustinol in Aspergillus nidulans.
abstract: Meroterpenoids are a class of fungal natural products that are produced from polyketide and terpenoid precursors. An understanding of meroterpenoid biosynthesis at the genetic level should facilitate engineering of second-generation molecules and increasing production of first-generation compounds. The filamentous fungus Aspergillus nidulans has previously been found to produce two meroterpenoids, austinol and dehydroaustinol. Using targeted deletions that we created, we have determined that, surprisingly, two separate gene clusters are required for meroterpenoid biosynthesis. One is a cluster of four genes including a polyketide synthase gene, ausA. The second is a cluster of 10 additional genes including a prenyltransferase gene, ausN, located on a separate chromosome. Chemical analysis of mutant extracts enabled us to isolate 3,5-dimethylorsellinic acid and 10 additional meroterpenoids that are either intermediates or shunt products from the biosynthetic pathway. Six of them were identified as novel meroterpenoids in this study. Our data, in aggregate, allow us to propose a complete biosynthetic pathway for the A. nidulans meroterpenoids.
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, California 90089, United States.
authors.forename: Hsien-Chun
authors.initials: HC
authors.lastname: Lo
authors.forename: Ruth
authors.initials: R
authors.lastname: Entwistle
authors.forename: Chun-Jun
authors.initials: CJ
authors.lastname: Guo
authors.forename: Manmeet
authors.initials: M
authors.lastname: Ahuja
authors.forename: Edyta
authors.initials: E
authors.lastname: Szewczyk
authors.forename: Jui-Hsiang
authors.initials: JH
authors.lastname: Hung
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Chiang
authors.forename: Berl R
authors.initials: BR
authors.lastname: Oakley
authors.forename: Clay C C
authors.initials: CC
authors.lastname: Wang
mesh_terms: D001233:Aspergillus nidulans / Q000235:genetics / Q000378:metabolism*; D055162:Biocatalysis; D002851:Chromatography, High Pressure Liquid; D004122:Dimethylallyltranstransferase / Q000378:metabolism; D017353:Gene Deletion; D005800:Genes, Fungal; D005810:Multigene Family; D009154:Mutation; D016366:Open Reading Frames; D013729:Terpenes / Q000378:metabolism*
chemical_list: D013729:Terpenes; C573071:austinol; D004122:Dimethylallyltranstransferase