Abstract
Fungi comprise a vast group of microorganisms including the Ascomycota (majority of all described fungi), the Basidiomycota (mushrooms or higher fungi), and the Zygomycota and Chytridiomycota (basal or lower fungi) that produce industrially interesting secondary metabolites, such as β-lactam antibiotics. These compounds are one of the most commonly prescribed drugs world-wide. Since Fleming's initial discovery of Penicillium notatum 80 years ago, the role of Penicillium as an antimicrobial source became patent. After the isolation of Penicillium chrysogenum NRRL 1951 six decades ago, classical mutagenesis and screening programs led to the development of industrial strains with increased productivity (at least three orders of magnitude). The new “omics” era has provided the key to understand the underlying mechanisms of the industrial strain improvement process. The review of different proteomics methods applied to P. chrysogenum has revealed that industrial modification of this microorganism was a consequence of a careful rebalancing of several metabolic pathways. In addition, the secretome analysis of P. chrysogenum has opened the door to new industrial applications for this versatile filamentous fungus.
Highlights
IntroductionLife comprises three domains: the bacteria, the archaea, and the eukaryota. Within the last one, the fungi kingdom forms a monophyletic group of the eukaryotic crown group, which collects the largest group of organisms [1]
Evolution of Fungi in Penicillin ProductionLife comprises three domains: the bacteria, the archaea, and the eukaryota
The vast knowledge accumulated along decades about the P. chrysogenum metabolism, and penicillin production contrasts with the scare information generated about methodology related with the “omics” approach, with proteomics
Summary
Life comprises three domains: the bacteria, the archaea, and the eukaryota. Within the last one, the fungi kingdom forms a monophyletic group of the eukaryotic crown group, which collects the largest group of organisms [1]. High-producing strains contain several copies of the penicillin cluster, it has been reported that penicillin production does not follow a linear correlation with the biosynthetic gene copy number, the transcript, or enzyme levels [36, 45,46,47], indicating that other modifications are playing an important role One of those modifications has been characterized in detail and is related to the catabolism of phenylacetic acid (the benzylpenicillin side chain precursor). The catabolism of phenylacetic acid through the homogentisate pathway is diminished in Wisconsin 54–1255 and, presumably, in derived strains as well, leading to a reduced degradation of phenylacetic acid and to penicillin overproduction [52] (Figure 2(b)) The importance of this enzyme in penicillin production was highlighted after the comparative analysis of the pahA gene of P. notatum (the Fleming’s isolate) and P. chrysogenum NRRL 1951 (the wildtype strain isolated in Peoria). The proteomics approach through the intracellular proteome analysis has added more relevant information about the events that led to create “domesticated” strains, which are the current high penicillin producer strains
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