delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase is a rate limiting enzyme for penicillin production in Aspergillus nidulans

Mol Gen Genet. 1996 Nov 27;253(1-2):189-97. doi: 10.1007/s004380050312.


The acvA gene from Aspergillus nidulans encoding delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) synthetase was overexpressed by replacing the wild-type acvA promoter with the ethanol dehydrogenase promoter, alcAp, from A. nidulans. The expression level of alcAp was determined using a strain in which the reporter gene, lacZ, is under the control of alcAp, and was found to be up to 100 times greater than that from the acvA promoter when induced in fermentation conditions. Penicillin yields were found to increase by as much as 30-fold when the acvA gene was overexpressed. Glucose, which strongly represses transcription from alcAp, also repressed penicillin biosynthesis in the overexpression strain. These results prove that ACV synthetase is a rate limiting enzyme for penicillin production in A. nidulans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Dehydrogenase / genetics
  • Aspergillus nidulans / enzymology*
  • Aspergillus nidulans / genetics
  • Culture Media
  • Fermentation
  • Gene Expression Regulation, Fungal
  • Genes, Fungal
  • Genes, Reporter
  • Glucose / pharmacology
  • Mutagenesis, Site-Directed
  • Penicillins / biosynthesis*
  • Peptide Synthases / genetics
  • Peptide Synthases / metabolism*
  • Promoter Regions, Genetic
  • Recombinant Fusion Proteins / biosynthesis
  • Transformation, Genetic


  • Culture Media
  • Penicillins
  • Recombinant Fusion Proteins
  • Alcohol Dehydrogenase
  • Peptide Synthases
  • alpha-aminoadipyl-cysteinyl-valine synthetase
  • Glucose