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Title

Phosphoribosyl pyrophosphate synthetase activity affects growth and riboflavin production in Ashbya gossypii

AuthorsJiménez, Alberto ; Santos García, María Ángeles; Revuelta Doval, José Luis
KeywordsPhosphoribosyl pyrophosphate
PRPP
Ashbya gossypii
Issue Date9-Sep-2008
PublisherBioMed Central
CitationBMC Biotechnology 2008, 8:67
AbstractBackground Phosphoribosyl pyrophosphate (PRPP) is a central compound for cellular metabolism and may be considered as a link between carbon and nitrogen metabolism. PRPP is directly involved in the de novo and salvage biosynthesis of GTP, which is the immediate precursor of riboflavin. The industrial production of this vitamin using the fungus Ashbya gossypii is an important biotechnological process that is strongly influenced by substrate availability. Results Here we describe the characterization and manipulation of two genes of A. gossypii encoding PRPP synthetase (AGR371C and AGL080C). We show that the AGR371C and AGL080C gene products participate in PRPP synthesis and exhibit inhibition by ADP. We also observed a major contribution of AGL080C to total PRPP synthetase activity, which was confirmed by an evident growth defect of the Δagl080c strain. Moreover, we report the overexpression of wild-type and mutant deregulated isoforms of Agr371cp and Agl080cp that significantly enhanced the production of riboflavin in the engineered A. gossypii strains. Conclusion It is shown that alterations in PRPP synthetase activity have pleiotropic effects on the fungal growth pattern and that an increase in PRPP synthetase enzymatic activity can be used to enhance riboflavin production in A. gossypii.
DescriptionAdditional files: Additional file 1: List of primers used in this study Additional file 2: Alignments of PRS proteins. Underlined in red are the residues involved in ribose-5-phosphate binding; underlined in blue are the residues involved in pyrophosphate binding. Red circles indicate residues that have been described to participate in catalysis in the B. subtilis, E. coli and human PRPP synthetases
Publisher version (URL)http://dx.doi.org/10.1186/1472-6750-8-67
URIhttp://hdl.handle.net/10261/8270
DOIhttp://dx.doi.org/10.1186/1472-6750-8-67
ISSN1472-6750
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