title: Increased production of inosine and guanosine by means of metabolic engineering of the purine pathway in Ashbya gossypii.
abstract: BACKGROUND
  Inosine and guanosine monophosphate nucleotides are convenient sources of the umami flavor, with attributed beneficial health effects that have renewed commercial interest in nucleotide fermentations. Accordingly, several bacterial strains that excrete high levels of inosine and guanosine nucleosides are currently used in the food industry for this purpose.
  
  
  RESULTS
  In the present study, we show that the filamentous fungus Ashbya gossypii, a natural riboflavin overproducer, excretes high amounts of inosine and guanosine nucleosides to the culture medium. Following a rational metabolic engineering approach of the de novo purine nucleotide biosynthetic pathway, we increased the excreted levels of inosine up to 27-fold.
  
  
  CONCLUSIONS
  We generated Ashbya gossypii strains with improved production titers of inosine and guanosine. Our results point to Ashbya gossypii as the first eukaryotic microorganism representing a promising candidate, susceptible to further manipulation, for industrial nucleoside fermentation.
authors.affiliation: Departamento de Microbiología y Genética, Metabolic Engineering Group, Universidad de Salamanca, Laboratory 323, Edificio Departamental, Campus Miguel de Unamuno, 37007, Salamanca, Spain. rodrigoledesma@usal.es.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Ledesma-Amaro
authors.affiliation: Departamento de Microbiología y Genética, Metabolic Engineering Group, Universidad de Salamanca, Laboratory 323, Edificio Departamental, Campus Miguel de Unamuno, 37007, Salamanca, Spain. ruben.martinez@usal.es.
authors.forename: Ruben M
authors.initials: RM
authors.lastname: Buey
authors.affiliation: Departamento de Microbiología y Genética, Metabolic Engineering Group, Universidad de Salamanca, Laboratory 323, Edificio Departamental, Campus Miguel de Unamuno, 37007, Salamanca, Spain. revuelta@usal.es.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Revuelta
mesh_terms: D000265:Adenylosuccinate Synthase / Q000235:genetics / Q000378:metabolism; D053898:Biosynthetic Pathways / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D055169:Eremothecium / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006151:Guanosine / Q000096:biosynthesis*; D007168:IMP Dehydrogenase / Q000235:genetics / Q000378:metabolism; D007288:Inosine / Q000096:biosynthesis*; D060847:Metabolic Engineering / Q000379:methods*; D009154:Mutation; D011683:Purine-Nucleoside Phosphorylase / Q000235:genetics / Q000378:metabolism; D011687:Purines / Q000096:biosynthesis; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D005656:Fungal Proteins; D011687:Purines; D006151:Guanosine; D007288:Inosine; D007168:IMP Dehydrogenase; D011683:Purine-Nucleoside Phosphorylase; D000265:Adenylosuccinate Synthase; C030985:purine