Academic
Publications
Why did the Fleming strain fail in penicillin industry?

Why did the Fleming strain fail in penicillin industry?,10.1016/j.fgb.2005.01.014,Fungal Genetics and Biology,Marta Rodríguez-Sáiz,Bruno Díez,José Lui

Why did the Fleming strain fail in penicillin industry?   (Citations: 4)
BibTex | RIS | RefWorks Download
Penicillin, discovered 75 years ago by Sir Alexander Fleming in Penicillium notatum, laid the foundations of modern antibiotic chemotherapy. Early work was carried out on the original Fleming strain, but it was later replaced by overproducing strains of Penicillium chrysogenum, which became the industrial penicillin producers. We show how a C1357→T (A394V) change in the gene encoding PahA in P. chrysogenum may help to explain the drawback of P. notatum. PahA is a cytochrome P450 enzyme involved in the catabolism of phenylacetic acid (PA; a precursor of penicillin G). We expressed the pahA gene from P. notatum in P. chrysogenum obtaining transformants able to metabolize PA (P. chrysogenum does not), and observing penicillin production levels about fivefold lower than that of the parental strain. Our data thus show that a loss of function in P. chrysogenum PahA is directly related to penicillin overproduction, and support the historic choice of P. chrysogenum as the industrial producer of penicillin.
Journal: Fungal Genetics and Biology - FUNGAL GENET BIOL , vol. 42, no. 5, pp. 464-470, 2005
Cumulative Annual
View Publication
The following links allow you to view full publications. These links are maintained by other sources not affiliated with Microsoft Academic Search.
    • ...Although this catabolic route has been described in P. chrysogenum [25,26] little is known about the pleiotropic effects of PAA on P. chrysogenum...

    Diana M Harriset al. Exploring and dissecting genome-wide gene expression responses of Peni...

    • ... the degree of expression of the penicillin biosynthesis genes, which is controlled by cis-acting regulatory sequences and trans-acting transcriptional factors, is the main cause for the diVerent penicillin production levels in these strains (Brakhage 1998; Martín 2000), although other factors, such as antibiotic secretion (Martín et al. 2005) or a loss of function of a cytochrome P450 involved in the catabolism of phenylacetic acid ...
    • ...In the time course experiments on expression of pcbC and gdhA genes total RNA was extracted and hybridized with a 1.5 kb EcoRV hybrid probe containing 718 bp from gdhA and 732 bp from the pcbC gene (Rodríguez-Sáiz et al. 2005)...
    • ...Furthermore, a single mutation in the P. chrysogenum gene encoding PahA, a cytochrome P450 enzyme involved in the catabolism of phenylacetic acid, causes a loss of function in phenylacetic acid oxidation which helps to explain the lower penicillin production of P. notatum, where this precursor is largely degraded (Rodríguez-Sáiz et al. 2005)...

    Katarina Kosalkováet al. Binding of the PTA1 transcriptional activator to the divergent promote...

Sort by: