title: Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum.
abstract: Industrial penicillin production with the filamentous fungus Penicillium chrysogenum is based on an unprecedented effort in microbial strain improvement. To gain more insight into penicillin synthesis, we sequenced the 32.19 Mb genome of P. chrysogenum Wisconsin54-1255 and identified numerous genes responsible for key steps in penicillin production. DNA microarrays were used to compare the transcriptomes of the sequenced strain and a penicillinG high-producing strain, grown in the presence and absence of the side-chain precursor phenylacetic acid. Transcription of genes involved in biosynthesis of valine, cysteine and alpha-aminoadipic acid-precursors for penicillin biosynthesis-as well as of genes encoding microbody proteins, was increased in the high-producing strain. Some gene products were shown to be directly controlling beta-lactam output. Many key cellular transport processes involving penicillins and intermediates remain to be characterized at the molecular level. Genes predicted to encode transporters were strongly overrepresented among the genes transcriptionally upregulated under conditions that stimulate penicillinG production, illustrating potential for future genomics-driven metabolic engineering.
authors.affiliation: DSM Anti Infectives, PO Box 425, 2600 AK Delft, The Netherlands. Marco.Berg-van-den@DSM.com
authors.forename: Marco A
authors.initials: MA
authors.lastname: van den Berg
authors.forename: Richard
authors.initials: R
authors.lastname: Albang
authors.forename: Kaj
authors.initials: K
authors.lastname: Albermann
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Badger
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Daran
authors.forename: Arnold J M
authors.initials: AJ
authors.lastname: Driessen
authors.forename: Carlos
authors.initials: C
authors.lastname: Garcia-Estrada
authors.forename: Natalie D
authors.initials: ND
authors.lastname: Fedorova
authors.forename: Diana M
authors.initials: DM
authors.lastname: Harris
authors.forename: Wilbert H M
authors.initials: WH
authors.lastname: Heijne
authors.forename: Vinita
authors.initials: V
authors.lastname: Joardar
authors.forename: Jan A K W
authors.initials: JA
authors.lastname: Kiel
authors.forename: Andriy
authors.initials: A
authors.lastname: Kovalchuk
authors.forename: Juan F
authors.initials: JF
authors.lastname: Martín
authors.forename: William C
authors.initials: WC
authors.lastname: Nierman
authors.forename: Jeroen G
authors.initials: JG
authors.lastname: Nijland
authors.forename: Jack T
authors.initials: JT
authors.lastname: Pronk
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Roubos
authors.forename: Ida J
authors.initials: IJ
authors.lastname: van der Klei
authors.forename: Noël N M E
authors.initials: NN
authors.lastname: van Peij
authors.forename: Marten
authors.initials: M
authors.lastname: Veenhuis
authors.forename: Hans
authors.initials: H
authors.lastname: von Döhren
authors.forename: Christian
authors.initials: C
authors.lastname: Wagner
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wortman
authors.forename: Roel A L
authors.initials: RA
authors.lastname: Bovenberg
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods*; D005656:Fungal Proteins / Q000235:genetics*; D016681:Genome, Fungal / Q000235:genetics*; D008969:Molecular Sequence Data; D010400:Penicillin G / Q000378:metabolism*; D010408:Penicillium chrysogenum / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D005656:Fungal Proteins; D014157:Transcription Factors; D010400:Penicillin G