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

Metab Eng. 2003 Jan;5(1):42-8. doi: 10.1016/s1096-7176(03)00006-5.

Abstract

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.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipates / metabolism*
  • Bioreactors / microbiology
  • Cell Culture Techniques / methods*
  • Cephalosporins / biosynthesis*
  • Gene Expression Regulation, Enzymologic / physiology
  • Gene Expression Regulation, Fungal / physiology
  • Oxygen / metabolism*
  • Oxygen Consumption / physiology
  • Penicillium chrysogenum / enzymology
  • Penicillium chrysogenum / genetics*
  • Penicillium chrysogenum / metabolism*
  • Protein Engineering / methods
  • Recombinant Proteins
  • Solubility
  • Species Specificity
  • Streptomyces / classification
  • Streptomyces / enzymology
  • Streptomyces / genetics
  • Streptomyces / metabolism
  • beta-Lactams / metabolism*

Substances

  • Adipates
  • Cephalosporins
  • Recombinant Proteins
  • adipoyl-7-amino-3-deacetoxycephalosporanic acid
  • beta-Lactams
  • adipic acid
  • Oxygen