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Why did the Fleming strain fail in penicillin industry?

Marta Rodríguez-Sáiz1, Bruno Díez, José Luis Barredo

  • 1R&D Biology, Antibióticos S. A., Avenida de Antibióticos 59-61, E-24009 León, Spain.

Fungal Genetics and Biology : FG & B
|April 6, 2005
PubMed

Insights

A gene mutation in Penicillium chrysogenum explains why it produces more penicillin than Penicillium notatum. This finding supports the historical use of P. chrysogenum for industrial penicillin production.

Area of Science:

  • Microbiology
  • Biochemistry
  • Industrial Biotechnology

Background:

  • Penicillin, a cornerstone of antibiotic chemotherapy, was discovered in Penicillium notatum.
  • Industrial penicillin production later shifted to Penicillium chrysogenum due to its higher yield.
  • The genetic basis for this difference in penicillin yield remained unclear.

Purpose of the Study:

  • To investigate the genetic factors contributing to the difference in penicillin production between P. notatum and P. chrysogenum.
  • To elucidate the role of the PahA enzyme in phenylacetic acid metabolism and its impact on penicillin yield.

Main Methods:

  • Gene expression analysis of the PahA gene in both P. notatum and P. chrysogenum.
  • Metabolic studies of phenylacetic acid (PA) in transformant strains.
  • Quantification of penicillin production in engineered P. chrysogenum strains.

Main Results:

  • A specific mutation (C1357\[T (A394V)]) in the P. chrysogenum PahA gene was identified.
  • Expression of the P. notatum pahA gene in P. chrysogenum enabled PA metabolism, which the parental strain cannot do.
  • Transformant strains exhibited a fivefold reduction in penicillin production compared to the wild-type P. chrysogenum.

Conclusions:

  • Loss of function in P. chrysogenum PahA due to the identified mutation is directly linked to penicillin overproduction.
  • This finding provides a molecular explanation for the historical selection of P. chrysogenum as the industrial penicillin producer.

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