ArticleMolecular genetics and genomics : MGG2004
Expression of cefD2 and the conversion of isopenicillin N into penicillin N by the two-component epimerase system are rate-limiting steps in cephalosporin biosynthesis.
Article in Molecular genetics and genomics : MGG, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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5 citing papers in PubMed, 23 citations in OpenAlex.
- Enhancing the β-Oxidation-Like Pathway for the Optimal Production of the Immunosuppressant Mycophenolic Acid.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Subcellular localization of fungal specialized metabolites.Fungal biology and biotechnology · 2022Review
- Comparative genomics of Alexander Fleming's original Penicillium isolate (IMI 15378) reveals sequence divergence of penicillin synthesis genes.Scientific reports · 2020Article
- Roles of 2-oxoglutarate oxygenases and isopenicillin N synthase in β-lactam biosynthesis.Natural product reports · 2018Review
- Expression of the Acremonium chrysogenum cefT gene in Penicillum chrysogenum indicates that it encodes an hydrophilic beta-lactam transporter.Current genetics · 2008Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
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Abstract
The conversion of isopenicillin N into penicillin N in Acremonium chrysogenum is catalyzed by an epimerization system that involves an isopenicillin N-CoA synthethase and isopenicillin N-CoA epimerase, encoded by the genes cefD1 and cefD2. Several transformants containing two to seven additional copies of both genes were obtained. Four of these transformants (TMCD26, TMCD53, TMCD242 and TMCD474) showed two-fold higher IPN epimerase activity than the untransformed A. chrysogenum C10, and produced 80 to 100% more cephalosporin C and deacetylcephalosporin C than the parental strain. A second class of transformants, including TMCD2, TMCD32 and TMCD39, in contrast, showed a drastic reduction in cephalosporin biosynthesis relative to the untransformed control. These transformants had no detectable IPN epimerase activity and did not produce cephalosporin C or deacetylcephalosporin C. They also expressed both endogenous and exogenous cefD2 genes only after long periods (72-96 h) of incubation, as shown by Northern analysis, and were impaired in mycelial branching in liquid cultures. The negative effect of amplification of the cefD1 - cefD2 gene cluster in this second class of transformants is not correlated with high gene dosage, but appears to be due to exogenous DNA integration into a specific locus, which results in a pleiotropic effect on growth and cefD2 expression.
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