caa a22 4500 605500916 CHVBK 20210128100558.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s00253-015-6710-2 doi (NATIONALLICENCE)springer-10.1007/s00253-015-6710-2 Increased riboflavin production by manipulation of inosine 5′-monophosphate dehydrogenase in Ashbya gossypii [Elektronische Daten] [Rubén Buey, Rodrigo Ledesma-Amaro, Mónica Balsera, José de Pereda, José Revuelta] Guanine nucleotides are the precursors of essential biomolecules including nucleic acids and vitamins such as riboflavin. The enzyme inosine-5′-monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step in the guanine nucleotide de novo biosynthetic pathway and plays a key role in controlling the cellular nucleotide pools. Thus, IMPDH is an important metabolic bottleneck in the guanine nucleotide synthesis, susceptible of manipulation by means of metabolic engineering approaches. Herein, we report the functional and structural characterization of the IMPDH enzyme from the industrial fungus Ashbya gossypii. Our data show that the overexpression of the IMPDH gene increases the metabolic flux through the guanine pathway and ultimately enhances 40% riboflavin production with respect to the wild type. Also, IMPDH disruption results in a 100-fold increase of inosine excretion to the culture media. Our results contribute to the developing metabolic engineering toolbox aiming at improving the production of metabolites with biotechnological interest in A. gossypii. Springer-Verlag Berlin Heidelberg, 2015 Ashbya gossypii nationallicence Metabolic engineering nationallicence Riboflavin nationallicence Inosine 5′-monophosphate dehydrogenase nationallicence Buey Rubén Metabolic Engineering Group, Departamento de Microbiología y Genética, Universidad de Salamanca, Edificio Departamental, Campus Miguel de Unamuno, 37007, Salamanca, Spain aut Ledesma-Amaro Rodrigo aut Balsera Mónica Department Abiotic Stress, Instituto de Recursos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas, C/ Cordel de Merinas 40-52, 37008, Salamanca, Spain aut de Pereda José Instituto de Biología Celular y Molecular del Cáncer, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Campus Miguel de Unamuno, 37007, Salamanca, Spain aut Revuelta José Metabolic Engineering Group, Departamento de Microbiología y Genética, Universidad de Salamanca, Edificio Departamental, Campus Miguel de Unamuno, 37007, Salamanca, Spain aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/22(2015-11-01), 9577-9589 0175-7598 99:22<9577 2015 99 253 https://doi.org/10.1007/s00253-015-6710-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00253-015-6710-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Buey Rubén Metabolic Engineering Group, Departamento de Microbiología y Genética, Universidad de Salamanca, Edificio Departamental, Campus Miguel de Unamuno, 37007, Salamanca, Spain aut NATIONALLICENCE 700 1- Ledesma-Amaro Rodrigo aut NATIONALLICENCE 700 1- Balsera Mónica Department Abiotic Stress, Instituto de Recursos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas, C/ Cordel de Merinas 40-52, 37008, Salamanca, Spain aut NATIONALLICENCE 700 1- de Pereda José Instituto de Biología Celular y Molecular del Cáncer, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Campus Miguel de Unamuno, 37007, Salamanca, Spain aut NATIONALLICENCE 700 1- Revuelta José Metabolic Engineering Group, Departamento de Microbiología y Genética, Universidad de Salamanca, Edificio Departamental, Campus Miguel de Unamuno, 37007, Salamanca, Spain aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/22(2015-11-01), 9577-9589 0175-7598 99:22<9577 2015 99 253