A metabolome study of the steady-state relation between central metabolism, amino acid biosynthesis and penicillin production in Penicillium chrysogenum

Nasution, U.; Gulik, Walter M. van; Ras, Cor; Proell, Angela M.; Heijnen, Joseph J.

doi:10.1016/j.ymben.2007.07.001

Cited by 70 publications

(51 citation statements)

References 16 publications

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“…Cysteine biosynthesis seems to be one of the major improvements that occurred during the selection process. Penicillin production flux is greatly influenced by cysteine availability for ACV formation (62). Cysteine synthase (forming cysteine from serine) is overrepresented in the Wis 54-1255 compared with the wild-type strain.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it has been reported that penicillin production is greatly influenced by the ATP level and cysteine concentration. Because NADPH is required for the biosynthesis of this amino acid, there is a positive relationship between cysteine and NADPH levels and penicillin production (62). NADPH is also required to reduce the oxidized glutathione during oxidative stress that results from intense aeration rates (30).…”

Section: Discussionmentioning

confidence: 99%

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Proteome Analysis of the Penicillin Producer Penicillium chrysogenum

Jami

Barreiro

Garcı́a-Estrada

et al. 2010

Molecular & Cellular Proteomics

119

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Proteomics is a powerful tool to understand the molecular mechanisms causing the production of high penicillin titers by industrial strains of the filamentous fungus Penicillium chrysogenum as the result of strain improvement programs. Penicillin biosynthesis is an excellent model system for many other bioactive microbial metabolites. The recent publication of the P. chrysogenum genome has established the basis to understand the molecular processes underlying penicillin overproduction. We report here the proteome reference map of P. chrysogenum Wisconsin 54-1255 (the genome project reference strain) together with an in-depth study of the changes produced in three different strains of this filamentous fungus during industrial strain improvement. Two-dimensional gel electrophoresis, peptide mass fingerprinting, and tandem mass spectrometry were used for protein identification. Around 1000 spots were visualized by "blue silver" colloidal Coomassie staining in a non-linear pI range from 3 to 10 with high resolution, which allowed the identification of 950 proteins (549 different proteins and isoforms). Comparison among the cytosolic proteomes of the wild-type NRRL 1951, Wisconsin 54-1255 (an improved, moderate penicillin producer), and AS-P-78 (a penicillin high producer) strains indicated that global metabolic reorganizations occurred during the strain improvement program. The main changes observed in the high producer strains were increases of cysteine biosynthesis (a penicillin precursor), enzymes of the pentose phosphate pathway, and stress response proteins together with a reduction in virulence and in the biosynthesis of other secondary metabolites different from penicillin (pigments and isoflavonoids). In the wild-type strain, we identified enzymes to utilize cellulose, sorbitol, and other carbon sources that have been lost in the high penicillin producer strains. Changes in the levels of a few specific proteins correlated well with the improved penicillin biosynthesis in the high producer strains. These results provide useful information to improve the production of many other bioactive secondary metabolites. Molecular & Cellular Proteomics 9:1182-1198, 2010.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Proteome Analysis of the Penicillin Producer Penicillium chrysogenum

Jami

Barreiro

Garcı́a-Estrada

et al. 2010

Molecular & Cellular Proteomics

119

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“…28 On the other hand, other phenomena besides genes expression could be responsible for the antibiotic production. Nasutation et al 29 have shown from a penicillin producing strain in glucose-limited chemostat cultures that the penicillin production flux appears to be mostly influenced by cystein, one of the three precursor amino acids, and by energy and redox cofactors. The relation between the low penicillin production flux and the low ATP and NADPH levels could be a possible explanation for the present results.…”

Section: Discussionmentioning

confidence: 99%

Effect of phenolic compounds and osmotic stress on the expression of penicillin biosynthetic genes from Penicillium chrysogenum var. halophenolicum strain

Guedes

Leitão

2012

J Xenobiotics

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Phenol and phenolic compounds are aromatic pollutants that inhibit biological treatment of wastewaters. Penicillium chrysogenum var. halophenolicum is a halotolerant fungus that previously showed the ability to degrade phenol and resorcinol in high salinity conditions. The presence of the penicillin biosynthetic cluster in P. chrysogenum var. halophenolicum was recently described. In this article, we examined the expression of pcbAB, pcbC and penDE, genes responsible for δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine synthetase, isopenicillin N synthase and isopenicillin N acyltransferase activities, respectively, in P. chrysogenum var. halophenolicum. A quantitative PCR (qPCR) approach was used to determine how these genes were expressed in media with 2% and 5.9% NaCl supplemented with phenol, catechol, hydroquinone and resorcinol as the sole carbon source. The effect of salt on the capability of P. chrysogenum var. halophenolicum to degrade aromatic compounds was measured using HPLC. qPCR analysis of RNA extracted from P. chrysogenum var. halophenolicum indicated that the expression levels of pcbAB, pcbC and penDE decreased in high saline concentrations compared to the levels expressed in media with glucose. High concentrations of salt significantly repress the expression of pcbAB and penDE. The pcbC gene was expressed differentially in catechol containing medium. There was no evident relationship between the expression levels of penicillin biosynthetic genes and yields of penicillin. Meanwhile, the presence of phenol and phenolic compounds seems to positively influence the antibiotic production; high concentrations of salt stimulated penicillin production. These results support the hypothesis that phenol, phenolic compounds and high concentrations of salt could act like a stress factor for P. chrysogenum var. halophenolicum resulting in higher yields of β-lactam antibiotic production.

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“…Successful applications cover a broad range of research topics and microbial systems, for example, in vivo NMR [23], optimization of amino acid formation [70,71], investigation of ethanol formation in yeast [72] and beta-lactam antibiotics [73][74][75].…”

Section: Application Of Microbial Metabolomicsmentioning

confidence: 99%

Metabolomics in Biotechnology (Microbial Metabolomics)

Oldiges

Noack

Paczia

2013

Metabolomics in Practice

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IntroductionThe first documentation of the term metabolomics goes back to two independent publications in 1998 and was used in the context of describing the metabolic behavior of microbial systems, showing a distinct phenotype regarding their physiology and extracellular metabolite spectrum [1,2]. For sure, these were not the first publications with such research activity, but these were the ones which obviously coined the term metabolomics. Later on, this term was picked up by the scientific community not only for the microbial field but also for many other scientific areas and paved its way to become one of the representatives of the omics era. In this sense, the suffix -ome is ''used to direct attention to holistic abstractions, an eventual goal, of which only a few parts may be initially in hand'' [3] and its origin goes back to the early twentieth century. Initially, the German botanist Hans Winkler is attributed to have coined the term genome by the combination of the terms gene and chromosome (Greek word soma = body) [4]. This keyword functioned as blueprint for the many other -omes that are currently investigated. Finally, they all go back to the Greek word soma and in opposite to the genome this term seems to be not precisely fitting for the metabolome, as the metabolites are not located or arranged in a body, but are distributed all over the system.Since 1998, the term metabolomics was increasingly used in the literature showing significant increase (Figure 15.1) and indicating the fast development of the field.The field of microbial metabolomics can be subdivided into the investigation of the endo-and exo-metabolome (intra-vs extracellular) as well as different approaches such as target analysis, metabolic profiling, and metabolic finger-/footprinting (Figure 15.2) [5,6]. On the one hand, the target analysis aims at the quantitative analysis of substrate and/or product metabolites of a given metabolic conversion, whereas metabolic profiling focuses on the quantitative analysis of a set of predefined metabolites belonging to a class of compounds or members of particular pathways or a linked group of metabolites (e.g., sugars, sugar phosphates, lipids, organic acids). On the other hand, metabolic Metabolomics in Practice: Successful Strategies to Generate and Analyze Metabolic Data, First Edition. Edited by Michael Lämmerhofer and Wolfram Weckwerth.

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A metabolome study of the steady-state relation between central metabolism, amino acid biosynthesis and penicillin production in Penicillium chrysogenum

Cited by 70 publications

References 16 publications

Proteome Analysis of the Penicillin Producer Penicillium chrysogenum

Proteome Analysis of the Penicillin Producer Penicillium chrysogenum

Effect of phenolic compounds and osmotic stress on the expression of penicillin biosynthetic genes from Penicillium chrysogenum var. halophenolicum strain

Metabolomics in Biotechnology (Microbial Metabolomics)

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