Influence of the adipate and dissolved oxygen concentrations on the beta-lactam production during continuous cultivations of a Penicillium chrysogenum strain expressing the expandase gene from Streptomyces clavuligerus.
The influence of adipate concentration and dissolved oxygen on production of adipoyl-7-aminodeacetoxycephalosporanic acid (ad-7-ADCA) by a recombinant strain of Penicillium chrysogenum expressing the expandase gene from Streptomyces clavuligerus was studied in glucose-limited continuous cultures. Operating conditions were maintained constant but the adipate and dissolved oxygen concentrations (DOC) were varied separately in a range from 1 to 37.5gl(-1) and from 2% to 125% air saturation (%AS), respectively. The total beta-lactams specific productivity, r(ptotal), was not significantly changed for adipate concentrations from 5 to 25gl(-1), but the flux towards an unknown by-product decreased as the adipate concentration increased. Investigations at different DOC showed that r(ptotal) was stable around 18 micro molgDW(-1)h(-1) for DOC being in the range from 15 to 125%AS. When DOC was decreased from 15 to 7%AS, r(ptotal) increased to 25 micro molgDW(-1)h(-1), mainly due to a two-fold increase in the adipoyl-6-aminopenicillanic acid (ad-6-APA) specific productivity.
Robin
J
J
Center for Process Biotechnology, Technical University of Denmark, BioCentrum-DTU, Building 223, Room 208, DK-2800, Lyngby, Denmark.
Bonneau
S
S
Schipper
D
D
Noorman
H
H
Nielsen
J
J
D000272:Adipates / Q000378:metabolism*; D019149:Bioreactors / Q000382:microbiology; D018929:Cell Culture Techniques / Q000379:methods*; D002511:Cephalosporins / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D010408:Penicillium chrysogenum / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D015202:Protein Engineering / Q000379:methods; D011994:Recombinant Proteins; D012995:Solubility; D013045:Species Specificity; D013302:Streptomyces / Q000145:classification / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D047090:beta-Lactams / Q000378:metabolism*
D000272:Adipates; D002511:Cephalosporins; D011994:Recombinant Proteins; C424182:adipoyl-7-amino-3-deacetoxycephalosporanic acid; D047090:beta-Lactams; C029900:adipic acid; D010100:Oxygen