Expression of the transporter encoded by the cefT gene of Acremonium chrysogenum increases cephalosporin production in Penicillium chrysogenum.
By introduction of the cefEF genes of Acremonium chrysogenum and the cmcH gene of Streptomyces clavuligerus, Penicillium chrysogenum can be reprogrammed to form adipoyl-7-amino-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid (ad7-ACCCA), a carbamoylated derivate of adipoyl-7-aminodeacetoxy-cephalosporanic acid. The cefT gene of A. chrysogenum encodes a cephalosporin C transporter that belongs to the Major Facilitator Superfamily. Introduction of cefT into an ad7-ACCCA-producing P. chrysogenum strain results in an almost 2-fold increase in cephalosporin production with a concomitant decrease in penicillin by-product formation. These data suggest that cephalosporin production by recombinant P. chrysogenum strains is limited by the ability of the fungus to secrete these compounds.
Nijland
Jeroen G
JG
Department of Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, 9751 NN Haren, The Netherlands.
Kovalchuk
Andriy
A
van den Berg
Marco A
MA
Bovenberg
Roel A L
RA
Driessen
Arnold J M
AJ
D000164:Acremonium / Q000235:genetics* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D002511:Cephalosporins / Q000096:biosynthesis*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D016681:Genome, Fungal; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010406:Penicillins / Q000378:metabolism; D010408:Penicillium chrysogenum / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D014158:Transcription, Genetic
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D010406:Penicillins; C025163:cephalosporin C