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

Content Provider	Springer Nature Link
Author	Buey, Rubén M. Ledesma Amaro, Rodrigo Balsera, Mónica Pereda, José María Revuelta, José Luis
Copyright Year	2015
Abstract	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.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.
Starting Page	9577
Ending Page	9589
Page Count	13
File Format	PDF
ISSN	01757598
Journal	Applied Microbiology and Biotechnology
Volume Number	99
Issue Number	22
e-ISSN	14320614
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2015-07-07
Publisher Place	Berlin, Heidelberg
Access Restriction	Subscribed
Subject Keyword	Ashbya gossypii Metabolic engineering Riboflavin Inosine 5′-monophosphate dehydrogenase Microbiology Microbial Genetics and Genomics Biotechnology
Content Type	Text
Resource Type	Article
Subject	Medicine Applied Microbiology and Biotechnology Biotechnology

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