A Straightforward Approach to Synthesize 7-Aminocephalosporanic Acid In Vivo in the Cephalosporin C Producer Acremonium chrysogenum
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| Gepubliceerd in: | Journal of Fungi vol. 8, no. 5 (2022), p. 450 |
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| Andere auteurs: | , , , , |
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| Online toegang: | Citation/Abstract Full Text + Graphics Full Text - PDF |
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| 001 | 2670154485 | ||
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| 022 | |a 2309-608X | ||
| 024 | 7 | |a 10.3390/jof8050450 |2 doi | |
| 035 | |a 2670154485 | ||
| 045 | 2 | |b d20220101 |b d20221231 | |
| 100 | 1 | |a Lin, Xuemei |u Allgemeine und Molekulare Botanik, Ruhr-Universität Bochum, 44780 Bochum, Germany; <email>xuemei.lin@rub.de</email> (X.L.); <email>tim.dahlmann@rub.de</email> (T.A.D.) | |
| 245 | 1 | |a A Straightforward Approach to Synthesize 7-Aminocephalosporanic Acid In Vivo in the Cephalosporin C Producer <i>Acremonium chrysogenum</i> | |
| 260 | |b MDPI AG |c 2022 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a The pharmaceutical industry has developed various highly effective semi-synthetic cephalosporins, which are generated by modifying the side chains of the core molecule 7-aminocephalosporanic acid (7-ACA). In industrial productions, the 7-ACA nucleus is obtained in vitro from cephalosporin C (CPC) by chemical or enzymatic processes, which are waste intensive and associated with high production costs. Here, we used a transgenic in vivo approach to express bacterial genes for cephalosporin C acylase (CCA) in the CPC producer Acremonium chrysogenum. Western blot and mass spectrometry analyses verified that the heterologous enzymes are processed into α- and β-subunits in the fungal cell. Extensive HPLC analysis detected substrates and products of CCAs in both fungal mycelia and culture supernatants, with the highest amount of 7-ACA found in the latter. Using different incubation times, temperatures, and pH values, we explored the optimal conditions for the active bacterial acylase to convert CPC into 7-ACA in the culture supernatant. We calculated that the best transgenic fungal strains exhibit a one-step conversion rate of the bacterial acylase of 30%. Our findings can be considered a remarkable contribution to supporting future pharmaceutical manufacturing processes with reduced production costs. | |
| 651 | 4 | |a Germany | |
| 653 | |a Plasmids | ||
| 653 | |a Gene expression | ||
| 653 | |a Cephalosporins | ||
| 653 | |a Bacteria | ||
| 653 | |a Biocatalysts | ||
| 653 | |a Antibiotics | ||
| 653 | |a Cell culture | ||
| 653 | |a Cloning | ||
| 653 | |a Genetic engineering | ||
| 653 | |a Staphylococcus infections | ||
| 653 | |a Pharmaceutical industry | ||
| 653 | |a Gram-positive bacteria | ||
| 653 | |a Mass spectroscopy | ||
| 653 | |a Cephalosporin C | ||
| 653 | |a E coli | ||
| 653 | |a Gram-negative bacteria | ||
| 653 | |a Genomics | ||
| 653 | |a High-performance liquid chromatography | ||
| 653 | |a Penicillin | ||
| 653 | |a Enzymes | ||
| 653 | |a Proteins | ||
| 653 | |a Acremonium chrysogenum | ||
| 700 | 1 | |a Lambertz, Jan |u Plant Biochemistry, Ruhr-University Bochum, 44780 Bochum, Germany; <email>jan.lambertz@rub.de</email> (J.L.); <email>marc.m.nowaczyk@rub.de</email> (M.M.N.) | |
| 700 | 1 | |a Dahlmann, Tim A |u Allgemeine und Molekulare Botanik, Ruhr-Universität Bochum, 44780 Bochum, Germany; <email>xuemei.lin@rub.de</email> (X.L.); <email>tim.dahlmann@rub.de</email> (T.A.D.) | |
| 700 | 1 | |a Nowaczyk, Marc M |u Plant Biochemistry, Ruhr-University Bochum, 44780 Bochum, Germany; <email>jan.lambertz@rub.de</email> (J.L.); <email>marc.m.nowaczyk@rub.de</email> (M.M.N.) | |
| 700 | 1 | |a König, Burghard |u Koenig und Funk Biotech GmbH, 13156 Berlin, Germany; <email>bk@kfbiotech.de</email> | |
| 700 | 1 | |a Kück, Ulrich |u Allgemeine und Molekulare Botanik, Ruhr-Universität Bochum, 44780 Bochum, Germany; <email>xuemei.lin@rub.de</email> (X.L.); <email>tim.dahlmann@rub.de</email> (T.A.D.) | |
| 773 | 0 | |t Journal of Fungi |g vol. 8, no. 5 (2022), p. 450 | |
| 786 | 0 | |d ProQuest |t Biological Science Database | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/2670154485/abstract/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text + Graphics |u https://www.proquest.com/docview/2670154485/fulltextwithgraphics/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/2670154485/fulltextPDF/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |