Computing the various pathways of penicillin synthesis and their molar yields
| Autor: | Sascha Schäuble, Maria T. E. Prauße, Reinhard Guthke, Stefan Schuster |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Metabolic network Bioengineering Transsulfuration Penicillins Penicillium chrysogenum Models Biological Applied Microbiology and Biotechnology 03 medical and health sciences Computational chemistry medicine Computer Simulation Invariant (mathematics) biology Chemistry biology.organism_classification Anti-Bacterial Agents Biosynthetic Pathways Penicillin 030104 developmental biology Chemical engineering Penicillin synthesis Yield (chemistry) Flux (metabolism) Biotechnology medicine.drug |
| Zdroj: | Biotechnology and Bioengineering. 113:173-181 |
| ISSN: | 0006-3592 |
| Popis: | More than 80 years after its discovery, penicillin is still a widely used and commercially highly important antibiotic. Here, we analyse the metabolic network of penicillin synthesis in Penicillium chrysogenum based on the concept of elementary flux modes. In particular, we consider the synthesis of the invariant molecular core of the various subtypes of penicillin and the two major ways of incorporating sulfur: transsulfuration and direct sulfhydrylation. 66 elementary modes producing this invariant core are obtained. These show four different yields with respect to glucose, notably ½, 2/5, 1/3, and 2/7, with the highest yield of ½ occurring only when direct sulfhydrylation is used and α-aminoadipate is completely recycled. In the case of no recycling of this intermediate, we find the maximum yield to be 2/7. We compare these values with earlier literature values. Our analysis provides a systematic overview of the redundancy in penicillin synthesis and a detailed insight into the corresponding routes. Moreover, we derive suggestions for potential knockouts that could increase the average yield. Biotechnol. Bioeng. 2016;113: 173–181. © 2015 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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