Physiological characterisation of Penicillium chrysogenum strains expressing the expandase gene from Streptomyces clavuligerus during batch cultivations. Growth and adipoyl-7-aminodeacetoxycephalosporanic acid production

Appl Microbiol Biotechnol. 2001 Oct;57(3):357-62. doi: 10.1007/s002530100787.

Abstract

The production of adipoyl-7-aminodeacetoxy-cephalosporanic acid (ad-7-ADCA) was studied, using two recombinant strains of Penicillium chrysogenum carrying the expandase gene from Streptomyces clavuligerus. The adipoyl-side chain of this compound may easily be removed using an amidase; and this process therefore represents a new route for the production of 7-ADCA, which serves as a precursor for the production of many semi-synthetic cephalosporins. In this study, one low- and one high-yielding strains were characterised and the specific productivities of ad-7-ADCA and byproducts of the biosynthetic pathway were compared. The fluxes through the biosynthetic pathway were quantified and it was found that there was a 30% higher flux through the expandase in the high-yielding strain. In both strains, there was a significant degradation of adipate. Furthermore, the initial adipate concentration in batch cultures was shown to have a positive effect on the formation of ad-7-ADCA.

Publication types

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

MeSH terms

  • Adipates / metabolism
  • Cephalosporins / analysis
  • Cephalosporins / metabolism*
  • Fructose / metabolism
  • Gluconates / metabolism
  • Glucose / metabolism
  • Intramolecular Transferases / genetics
  • Intramolecular Transferases / metabolism*
  • Mutagenesis, Insertional
  • Penicillanic Acid / analogs & derivatives
  • Penicillanic Acid / analysis
  • Penicillanic Acid / metabolism
  • Penicillin-Binding Proteins*
  • Penicillium chrysogenum / genetics
  • Penicillium chrysogenum / metabolism
  • Penicillium chrysogenum / physiology*
  • Streptomyces / genetics
  • Sucrose / metabolism

Substances

  • Adipates
  • Cephalosporins
  • Gluconates
  • Penicillin-Binding Proteins
  • adipoyl-7-amino-3-deacetoxycephalosporanic acid
  • Fructose
  • Sucrose
  • adipic acid
  • Penicillanic Acid
  • Intramolecular Transferases
  • deacetoxycephalosporin C synthetase
  • Glucose
  • aminopenicillanic acid
  • gluconic acid