Expression of the transporter encoded by the cefT gene of Acremonium chrysogenum increases cephalosporin production in Penicillium chrysogenum

Nijland, Jeroen G.; Kovalchuk, Andriy; Berg, M. A.; Bovenberg, Roel A. L.; Driessen, Arnold J. M.

doi:10.1016/j.fgb.2008.07.008

Cited by 43 publications

(27 citation statements)

References 16 publications

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“…This is probably because that this strain has been already undergone several rounds of mutagenesis and the copy number of cefT has already been increased. Unlike a recent publication [24] that demonstrated cefT had a clearly positive effect on CPC production, our result showed that cefT was not a limiting factor in high CPC producer because strain 84-3-87 has a much higher original CPC yield than C10. Comparing transformants bearing pYG858 and pYG877, there is no significant improvement in CPC production when cefEF gene was introduced.…”

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confidence: 99%

Improvement of Cephalosporin C Production by Recombinant DNA Integration in Acremonium chrysogenum

Liu

Gong²,

Xie³

et al. 2009

Mol Biotechnol

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Cephalosporin is a β-lactam antibiotic produced by Acremonium chrysogenum using submerged fermentation. Carbon and nitrogen are the most influential medium ingredients for cephalosporin formation. The purpose of this study was to obtain the best composition of media for cephalosporin C production. Response surface methodology was used for production optimization. The results showed that molasses of 70 g/L was the best carbon source, while the best nitrogen source was the combination of corn steep liquor, urea and ammonium sulphate. DL-methionine, carbon, and nitrogen source significantly affected the production of cephalosporin C. The mathematically modelled optimization showed that the highest production of cephalosporin C (3876 mg/L) was obtained using medium composition of 68.28 g/L molasses, 71.61 g/L nitrogen, and 0.4 g/L DL-methionine. Laboratory verification using the same medium composition produced 3696 mg/L of cephalosporin C, being 4.65% different from the mathematically optimized results. Medium optimization increased the cephalosprin C production which was 1.48 times higher than that using the previous medium, where the maximum production was only 2487 mg / L. ABSTRAK Sefalosporin C adalah golongan antibiotik β-lactam yang dihasilkan Acremonium chrysogenum melalui fermentasi cair. Komponen yang sangat berpengaruh terhadap produksi sefalosporin C adalah sumber karbon dan nitrogen. Penelitian ini bertujuan mendapatkan komposisi media terbaik untuk produksi sefalosporin C. Optimasi dilakukan menggunakan metode respon permukaan. Hasil menunjukkan bahwa molases 70 g/L adalah sumber karbon terbaik dan kombinasi corn steep liquor, urea dan ammonium sulfat adalah sumber nitrogen terbaik. DL-methionin, sumber karbon, dan nitrogen berpengaruh nyata terhadap produksi sefalosporin C. Optimasi menggunakan model matematika menunjukkan produksi sefalosporin C tertinggi (3876 mg/L) yang diperoleh dengan komposisi media 68,28 g/L molases, 71,61 g/L nitrogen, dan 0,4 g/L DL-methionin. Verfikasi di laboratorium menggunakan komposisi media yang sama menghasilkan sefalosporin C sebesar 3696 mg/L, berbeda 4,65% dibanding dengan hasil optimasi matematis. Optimasi media mampu meningkatkan produksi sefalosprin C sebesar 1,48 kali dibanding media yang digunakan sebelumnya, dimana maksimal hanya menghasilkan 2487 mg/L.

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confidence: 99%

Improvement of Cephalosporin C Production by Recombinant DNA Integration in Acremonium chrysogenum

Liu

Gong²,

Xie³

et al. 2009

Mol Biotechnol

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“…Digested DNA fragments were separated on a 0.8 % agarose gel, blotted onto a Zeta-Probe membrane (Biorad) as described earlier [26], and hybridized with the indicated DIG labeled probes.…”

Section: Methodsmentioning

confidence: 99%

A Non-Canonical NRPS Is Involved in the Synthesis of Fungisporin and Related Hydrophobic Cyclic Tetrapeptides in Penicillium chrysogenum

et al. 2014

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The filamentous fungus Penicillium chrysogenum harbors an astonishing variety of nonribosomal peptide synthetase genes, which encode proteins known to produce complex bioactive metabolites from simple building blocks. Here we report a novel non-canonical tetra-modular nonribosomal peptide synthetase (NRPS) with microheterogenicity of all involved adenylation domains towards their respective substrates. By deleting the putative gene in combination with comparative metabolite profiling various unique cyclic and derived linear tetrapeptides were identified which were associated with this NRPS, including fungisporin. In combination with substrate predictions for each module, we propose a mechanism for a ‘trans-acting’ adenylation domain.

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“…Southern blotting was carried out by digesting gDNA (5 µg) with the indicated restriction enzymes. Digested DNA fragments were separated on a 0.8% agarose gel and blotted onto a Zeta-Probe membrane (Biorad) described earlier [27], and hybridized with the indicated probes that were DIG labeled.…”

Section: Methodsmentioning

confidence: 99%

A Branched Biosynthetic Pathway Is Involved in Production of Roquefortine and Related Compounds in Penicillium chrysogenum

et al. 2013

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Profiling and structural elucidation of secondary metabolites produced by the filamentous fungus Penicillium chrysogenum and derived deletion strains were used to identify the various metabolites and enzymatic steps belonging to the roquefortine/meleagrin pathway. Major abundant metabolites of this pathway were identified as histidyltryptophanyldiketopiperazine (HTD), dehydrohistidyltryptophanyldi-ketopiperazine (DHTD), roquefortine D, roquefortine C, glandicoline A, glandicoline B and meleagrin. Specific genes could be assigned to each enzymatic reaction step. The nonribosomal peptide synthetase RoqA accepts L-histidine and L-tryptophan as substrates leading to the production of the diketopiperazine HTD. DHTD, previously suggested to be a degradation product of roquefortine C, was found to be derived from HTD involving the cytochrome P450 oxidoreductase RoqR. The dimethylallyltryptophan synthetase RoqD prenylates both HTD and DHTD yielding directly the products roquefortine D and roquefortine C without the synthesis of a previously suggested intermediate and the involvement of RoqM. This leads to a branch in the otherwise linear pathway. Roquefortine C is subsequently converted into glandicoline B with glandicoline A as intermediates, involving two monooxygenases (RoqM and RoqO) which were mixed up in an earlier attempt to elucidate the biosynthetic pathway. Eventually, meleagrin is produced from glandicoline B involving a methyltransferase (RoqN). It is concluded that roquefortine C and meleagrin are derived from a branched biosynthetic pathway.

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Expression of the transporter encoded by the cefT gene of Acremonium chrysogenum increases cephalosporin production in Penicillium chrysogenum

Cited by 43 publications

References 16 publications

Improvement of Cephalosporin C Production by Recombinant DNA Integration in Acremonium chrysogenum

Improvement of Cephalosporin C Production by Recombinant DNA Integration in Acremonium chrysogenum

A Non-Canonical NRPS Is Involved in the Synthesis of Fungisporin and Related Hydrophobic Cyclic Tetrapeptides in Penicillium chrysogenum

A Branched Biosynthetic Pathway Is Involved in Production of Roquefortine and Related Compounds in Penicillium chrysogenum

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