Penicillin Yields From New Mold Strains

Backus, M. P.; Stauffer, J. F.; Johnson, Marvin J.

doi:10.1021/ja01205a518

Cited by 33 publications

(13 citation statements)

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“…P. chrysogenum Q176 was used exclusively in this study. Data regarding the origin of this strain and regarding the penicillin yields and types obtained by its use have already been published (Backus et al, 1946;Higuchi et al, 1946; Jarvis and Johnson, 1947; Winsten and Spark, 1947).…”

Section: Experimental Methodsmentioning

confidence: 99%

Evaluation of Precursors for Penicillin G

Singh

Johnson

1948

J Bacteriol

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Section: Experimental Methodsmentioning

confidence: 99%

Evaluation of Precursors for Penicillin G

Singh

Johnson

1948

J Bacteriol

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“…This strain was mutated by 275 nm ultraviolet irradiation of spores at the University of Wisconsin, and the Q-176 mutant was obtained. It was tested in 300-liter fermentors, yielding over 550 μ g/mL (900 i.u./mL) [27]. This strain represents the origin of the Wisconsin family of superior strains, some producing over 1800 μ g/mL (3000 i.u./mL) [28].…”

Section: Classical Strain Improvement and Molecular Genomic-transcmentioning

confidence: 99%

Proteomics Shows New Faces for the Old Penicillin ProducerPenicillium chrysogenum

Barreiro

Martı́n

Garcı́a-Estrada

2012

Journal of Biomedicine and Biotechnology

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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 ofPenicillium notatum80 years ago, the role ofPenicilliumas an antimicrobial source became patent. After the isolation ofPenicillium chrysogenumNRRL 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 toP. chrysogenumhas revealed that industrial modification of this microorganism was a consequence of a careful rebalancing of several metabolic pathways. In addition, the secretome analysis ofP. chrysogenumhas opened the door to new industrial applications for this versatile filamentous fungus.

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“…7b). This analysis was further extended by testing the producer strain Wisconsin 54-1255 (Elander, 1983) and its ancestor Q176 (Backus et al, 1946). With both liquid and solid media, Q176 showed the same growth phenotype as the two mutant strains.…”

Section: Modified Cell Wall Composition Of the Disrupted Pcchib1 Strainsmentioning

confidence: 99%

PcchiB1, encoding a class V chitinase, is affected by PcVelA and PcLaeA, and is responsible for cell wall integrity in Penicillium chrysogenum

et al. 2011

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Penicillin production in Penicillium chrysogenum is controlled by PcVelA and PcLaeA, two components of the regulatory velvet-like complex. Comparative microarray analysis with mutants lacking PcVelA or PcLaeA revealed a set of 62 common genes affected by the loss of both components. A downregulated gene in both knockout strains is PcchiB1, potentially encoding a class V chitinase. Under nutrient-depleted conditions, transcript levels of PcchiB1 are strongly upregulated, and the gene product contributes to more than 50 % of extracellular chitinase activity. Functional characterization by generating PcchiB1-disruption strains revealed that PcChiB1 is responsible for cell wall integrity and pellet formation in P. chrysogenum. Further, fluorescence microscopy with a DsRed-labelled chitinase suggests a cell wall association of the protein. An unexpected phenotype occurred when knockout strains were grown on media containing N-acetylglucosamine as the sole C and N source, where, in contrast to the recipient, a penicillin producer strain, the mutants and an ancestral strain show distinct mycelial growth. We discuss the relevance of this class V chitinase for morphology in an industrially important fungus. INTRODUCTIONPenicillium chrysogenum is the main industrial producer of the b-lactam antibiotic penicillin. In this filamentous ascomycete, developmental processes and secondary metabolism are tightly linked and controlled by diverse conserved regulators. Among these are PcVelA and PcLaeA, two global regulators, which have recently been shown to control penicillin biosynthesis as well as hyphal and conidiophore morphogenesis (Hoff et al., 2010a). Homologues of both proteins have been intensively studied in the model fungus Aspergillus nidulans (Calvo, 2008;Bok & Keller, 2004;Sarikaya Bayram et al., 2010). For example, it has been shown that both proteins, together with VelB, form the core of a regulatory heterotrimeric complex, which we refer to as the velvet complex (Bayram et al., 2008a). The general regulatory function of these proteins is highly conserved in diverse filamentous fungi (Calvo, 2008), and it has been shown that velvet-like complexes exist in other ascomycetes (Hoff et al., 2010a;Wiemann et al., 2010).Despite its importance for development and secondary metabolism, so far only a few high-throughput transcriptional analyses have been conducted with strains lacking components of the velvet complex. Cary et al. (2007) performed a microarray analysis with a DveA mutant of Aspergillus flavus to analyse the expression levels of 5002 genes. That study identified 136 differentially regulated genes in the disruption strain compared with the control strain, some of these representing known aflatoxin biosynthetic genes. In Aspergillus fumigatus, about 20-40 % of all secondary metabolite biosynthesis genes are negatively affected by the loss of laeA, as detected by whole-genome microarray analysis (Perrin et al., 2007).Using a PcvelA knockout strain, our previous microarray study to understand the expression profi...

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Penicillin Yields From New Mold Strains

Cited by 33 publications

References 0 publications

Evaluation of Precursors for Penicillin G

Evaluation of Precursors for Penicillin G

Proteomics Shows New Faces for the Old Penicillin ProducerPenicillium chrysogenum

PcchiB1, encoding a class V chitinase, is affected by PcVelA and PcLaeA, and is responsible for cell wall integrity in Penicillium chrysogenum

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