Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum.
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.
van den Berg
Marco A
MA
DSM Anti Infectives, PO Box 425, 2600 AK Delft, The Netherlands. Marco.Berg-van-den@DSM.com
Albang
Richard
R
Albermann
Kaj
K
Badger
Jonathan H
JH
Daran
Jean-Marc
JM
Driessen
Arnold J M
AJ
Garcia-Estrada
Carlos
C
Fedorova
Natalie D
ND
Harris
Diana M
DM
Heijne
Wilbert H M
WH
Joardar
Vinita
V
Kiel
Jan A K W
JA
Kovalchuk
Andriy
A
Martín
Juan F
JF
Nierman
William C
WC
Nijland
Jeroen G
JG
Pronk
Jack T
JT
Roubos
Johannes A
JA
van der Klei
Ida J
IJ
van Peij
Noël N M E
NN
Veenhuis
Marten
M
von Döhren
Hans
H
Wagner
Christian
C
Wortman
Jennifer
J
Bovenberg
Roel A L
RA
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*
D005656:Fungal Proteins; D014157:Transcription Factors; D010400:Penicillin G