Publication: Estudio del transporte de esteroides en Mycobacterium smegmatis mc²155 y sus aplicaciones biotecnológicas
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2017-05-11
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Universidad Complutense de Madrid
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Abstract
Debido a la importancia clínica, industrial y medio ambiental del colesterol, desde hace más de 70 años se han seleccionado microorganismos capaces de degradarlo (Söhngen, 1913; Turfitt, 1944), sin embargo hoy en día aún se desconocen gran parte de las bases genéticas y bioquímicas de las rutas de degradación de este compuesto. Dilucidar completamente estas rutas metabólicas permitiría desarrollar nuevos procesos biotecnológicos en la industria farmacéutica para la producción de esteroides. Por otro lado y dado que el colesterol se ha relacionado con la patogénesis de Mycobacterium tuberculosis (Pandey y Sassetti, 2008; Joshi et al., 2006), el estudio de estas rutas ha adquirido recientemente un elevado interés desde un punto de vista clínico. Aunque uno de los elementos claves del metabolismo bacteriano del colesterol es su transporte, hasta la fecha, el conocimiento sobre el transporte selectivo de esteroides en bacterias es escaso. Las bacterias que degradan colesterol poseen un operón denominado mce4 que codifica un sistema de tipo ABC responsable de su transporte al interior de la célula (Pandey y Sassetti, 2008; Mohn et al., 2008). Este operón contiene 10 genes, yrbE4ABmce4ABCDEFmas4AB, dos de los cuales codifican las permeasas del sistema y el resto, de función desconocida, se postula que codifican las proteínas de unión al sustrato. Además, la actividad ATPasa del sistema ABC es proporcionada por el gen mceG (MSMEG_1366) que codifica una enzima tipo Mkl, localizado lejos del operón mce4, y que comparte con otros sistemas Mce similares de función desconocida presentes en la misma célula (Joshi et al., 2006)...
Due to the clinical, industrial and environmental cholesterol importance, the microorganisms able to degrade it have been selected for more than 70 years (Söhngen, 1913; Turfitt, 1944) despite this fact, nowadays most of the genetic and biochemical basis of its degradation pathways are still unknown. The fully elucidation of these metabolic pathways would lead to the development of new biotechnological processes in the pharmaceutical industry for the production of steroids. Moreover and since cholesterol has been linked to the pathogenesis of Mycobacterium tuberculosis (Pandey and Sassetti, 2008; Joshi et al., 2006), the study of these routes has recently acquired a large interest from a clinical point of view. Although one of the key elements in the bacterial metabolism of cholesterol is the uptake process, the knowledge about the selective transport of steroids in bacteria is low. Bacteria able to degrade cholesterol possess an operon called mce4 that encodes an ABC system responsible for its transport into the cell (Pandey and Sassetti, 2008; Mohn et al., 2008). This operon contains 10 genes, yrbE4ABmce4ABCDEFmas4AB, two of which encode the permeases of the system and the rest, of unknown function, are postulated to encode the substrate binding proteins. Additionally, the ATPase activity of this ABC system is provided by the mceG gene (MSMEG_1366) encoding an Mkl enzyme that is located away from the mce4 operon and is shared with other Mce systems that are present in the same cell (Joshi et al., 2006)...
Due to the clinical, industrial and environmental cholesterol importance, the microorganisms able to degrade it have been selected for more than 70 years (Söhngen, 1913; Turfitt, 1944) despite this fact, nowadays most of the genetic and biochemical basis of its degradation pathways are still unknown. The fully elucidation of these metabolic pathways would lead to the development of new biotechnological processes in the pharmaceutical industry for the production of steroids. Moreover and since cholesterol has been linked to the pathogenesis of Mycobacterium tuberculosis (Pandey and Sassetti, 2008; Joshi et al., 2006), the study of these routes has recently acquired a large interest from a clinical point of view. Although one of the key elements in the bacterial metabolism of cholesterol is the uptake process, the knowledge about the selective transport of steroids in bacteria is low. Bacteria able to degrade cholesterol possess an operon called mce4 that encodes an ABC system responsible for its transport into the cell (Pandey and Sassetti, 2008; Mohn et al., 2008). This operon contains 10 genes, yrbE4ABmce4ABCDEFmas4AB, two of which encode the permeases of the system and the rest, of unknown function, are postulated to encode the substrate binding proteins. Additionally, the ATPase activity of this ABC system is provided by the mceG gene (MSMEG_1366) encoding an Mkl enzyme that is located away from the mce4 operon and is shared with other Mce systems that are present in the same cell (Joshi et al., 2006)...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, Departamento de Bioquímica y Biología Molecular, leída el 14/12/2015