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 I to 37.5 g l(-1) and from 2% to 125% air saturation (%AS), respectively. The total beta-lactams specific productivity, r(p) (total) was not significantly changed for adipate concentrations from 5 to 25 g l(-1), but the flux towards an unknown by-product decreased as the adipate concentration increased. Investigations at different DOC showed that r(p) (total) was stable around 18 mumol g DW-1 h(-1) for DOC being in the range from 15 to 125%AS. When DOC was decreased from 15 to 7%AS, r(p) (total) increased to 25 mumol g DW-1 h(-1), mainly due to a two-fold increase in the adipoyl-6-aminopenicillanic acid (ad-6-APA) specific productivity.