4XTD

Structure of the covalent intermediate E-XMP* of the IMP dehydrogenase of Ashbya gossypii

Summary for 4XTD

• Entry DOI: 10.2210/pdb4xtd/pdb
• Descriptor: Inosine-5'-monophosphate dehydrogenase,Inosine-5'-monophosphate dehydrogenase, INOSINIC ACID (3 entities in total)
• Functional Keywords: oxidoreductase, xmp
• Biological source: Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056) (Yeast); More
• Cellular location: Cytoplasm : Q756Z6
• Total number of polymer chains: 2
• Total formula weight: 89753.52

Authors

Buey, R.M.,Ledesma-Amaro, R.,Balsera, M.,de Pereda, J.M.,Revuelta, J.L. (deposition date: 2015-01-23, release date: 2015-07-22, Last modification date: 2024-01-10)

Primary citation

Buey, R.M.,Ledesma-Amaro, R.,Balsera, M.,de Pereda, J.M.,Revuelta, J.L.
Increased riboflavin production by manipulation of inosine 5'-monophosphate dehydrogenase in Ashbya gossypii.
Appl.Microbiol.Biotechnol., 99:9577-9589, 2015

PubMed 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 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.

PubMed: 26150243
DOI: 10.1007/s00253-015-6710-2

Experimental method

X-RAY DIFFRACTION (2.05 Å)