Increased riboflavin production by manipulation of inosine 5′-monophosphate dehydrogenase in Ashbya gossypii

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 ratelimiting step in the guanine nucleotide de novo biosynthetic pathway and plays a key role in controlli...

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Bibliographic Details
Published in:Applied microbiology and biotechnology 2015-11, Vol.99 (22), p.9577-9589
Main Authors: Buey, Rubén M, Ledesma-Amaro, Rodrigo, Balsera, Mónica, de Pereda, José María, Revuelta, José Luis
Format: Article
Language:English
Subjects:
Analysis
Ashbya gossypii
biochemical pathways
Biomedical and Life Sciences
Biosynthesis
Biotechnologically Relevant Enzymes and Proteins
Biotechnology
Culture media
Dehydrogenase
Dehydrogenases
Engineering
Enzyme kinetics
Enzymes
Eremothecium - enzymology
Eremothecium - genetics
Eremothecium - metabolism
Eremothecium gossypii
Excretion
Fungi
Gene Expression
gene overexpression
genes
Genetic engineering
guanine
guanine nucleotides
IMP Dehydrogenase - genetics
IMP Dehydrogenase - metabolism
Life Sciences
Metabolic Engineering
Metabolic Flux Analysis
Metabolism
Metabolites
Microbial Genetics and Genomics
Microbiology
Mold
Nucleic acids
Nucleotides
Purines
riboflavin
Riboflavin - biosynthesis
Signal transduction
Studies
Vitamin B
Vitamins
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Summary: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 ratelimiting 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.
ISSN:0175-7598
1432-0614
DOI:10.1007/s00253-015-6710-2