Papel de las Especies Reactivas de Oxígeno en la biosíntesis de Penicilina G, Cefalosporina C y Lovastatina
In previous work on the production of lovastatin by Aspergillus terreus, we found that the concentration of reactive oxygen species (ROS) increased to high levels precisely at the beginning of the production phase (idiophase) and that these levels were maintained throughout the idiophase. Furthermor...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | México |
| Institución: | Universidad Autónoma Metropolitana |
| Repositorio: | Repositorio Institucional de la UAM Iztapalapa |
| Idioma: | español |
| OAI Identifier: | oai:bindani.izt.uam.mx:pg15bf11c |
| Acceso en línea: | https://doi.org/10.24275/uami.pg15bf11c |
| Access Level: | acceso abierto |
| Palabra clave: | info:eu-repo/classification/LEM/Estrés oxidativo info:eu-repo/classification/LEM/Biosíntesis info:eu-repo/classification/LEM/Oxidative stress info:eu-repo/classification/LEM/Penicilina info:eu-repo/classification/LEM/Biotechnology info:eu-repo/classification/LEM/Biotecnología info:eu-repo/classification/LEM/Penicillin info:eu-repo/classification/LEM/Cefalosporina info:eu-repo/classification/LEM/Especies reactivas del oxígeno info:eu-repo/classification/LEM/Statins (Cardiovascular agents) info:eu-repo/classification/LEM/Cephalosporins info:eu-repo/classification/LEM/Lovastatina info:eu-repo/classification/LEM/Biosynthesis info:eu-repo/classification/cti/6 |
| Sumario: | In previous work on the production of lovastatin by Aspergillus terreus, we found that the concentration of reactive oxygen species (ROS) increased to high levels precisely at the beginning of the production phase (idiophase) and that these levels were maintained throughout the idiophase. Furthermore, ROS were shown to regulate lovastatin biosynthesis. Regulation by ROS has also been reported for aflatoxins. It has been suggested that, due to their antioxidant activity, aflatoxins are regulated and synthesized as a second line of defence against oxidative stress. To study the possible regulation of ROS of other secondary metabolites of industrial importance, we analysed the relationship between ROS and penicillin G biosynthesis by Penicillium chrysogenum and cephalosporin C biosynthesis by Acremonium chrysogenum. The results revealed a similar accumulation of ROS in the idiophase in the penicillin and cephalosporin fermentations. Furthermore, when the intracellular concentrations of ROS were decreased by adding antioxidants to the cultures, the production of penicillin and cephalosporin was drastically reduced. When intracellular ROS were increased by adding exogenous ROS (H2O2) to the cultures, proportional increases in penicillin and cephalosporin biosynthesis were obtained. Finally, we demonstrate that this increase and decrease in the production induced by the manipulation of ROS was due to the biosynthetic gene pcbcAB being over-expressed or repressed, in A. chrysogenum and P. chrysogenum. Thus, demonstrating that ROS regulate penicillin and cephalosporin biosynthesis at the transcriptional level. Furthermore, we analysed whether the levels of natural ROS determined the production capacity of secondary metabolites in different strains of the same species; and we found that the profile and levels of ROS are the same between high and low production strains, but the natural levels of ROS do vary between species. On the other hand, in the lovastatin model, it was also evaluated whether the transcription factors of oxidative-stress response SrrA and MsnA played a role in the regulation of lovastatin biosynthesis, induced by the accumulation of ROS; this was evaluated through silencing of these genes in A. terreus. The SisrrA mutants were found to have an effect only in submerged fermentation (SmF), where they produced more lovastatin, and there was a greater accumulation of ROS in idiophase. While the SimsnA, showed overproduction in SmF and SSF (Solid-State Fermentation), being in the latter where the increase was very large; however, the attenuation of msnA did not affect ROS levels. Our results provide evidence that regulation by ROS is a general mechanism that controls secondary metabolism in fungi. And, in the lovastatin model, SrrA and MsnA are part of the regulatory circuit, acting as negative regulators, and in the case of SrrA, their regulation is specific to SmF. |
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