TY  - JOUR
A1  - Peifer, Susanne
A1  - Barduhn, Tobias
A1  - Zimmet, Sarah
A1  - Volmer, Dietrich A.
A1  - Heinzle, Elmar
A1  - Schneider, Konstantin
T1  - Metabolic engineering of the purine biosynthetic pathway in Corynebacterium glutamicum results in increased intracellular pool sizes of IMP and hypoxanthine
T2  - Microbial cell factories
N2  - Background: Purine nucleotides exhibit various functions in cellular metabolism. Besides serving as building blocks for nucleic acid synthesis, they participate in signaling pathways and energy metabolism. Further, IMP and GMP represent industrially relevant biotechnological products used as flavor enhancing additives in food industry. Therefore, this work aimed towards the accumulation of IMP applying targeted genetic engineering of Corynebacterium glutamicum.
Results: Blocking of the degrading reactions towards AMP and GMP lead to a 45-fold increased intracellular IMP pool of 22 mumol gCDW-1. Deletion of the pgi gene encoding glucose 6-phosphate isomerase in combination with the deactivated AMP and GMP generating reactions, however, resulted in significantly decreased IMP pools (13 mumol gCDW-1). Targeted metabolite profiling of the purine biosynthetic pathway further revealed a metabolite shift towards the formation of the corresponding nucleobase hypoxanthine (102 mumol gCDW-1) derived from IMP degradation.
Conclusions: The purine biosynthetic pathway is strongly interconnected with various parts of the central metabolism and therefore tightly controlled. However, deleting degrading reactions from IMP to AMP and GMP significantly increased intracellular IMP levels. Due to the complexity of this pathway further degradation from IMP to the corresponding nucleobase drastically increased suggesting additional targets for future strain optimization.
KW  - Purine accumulation
KW  - Metabolic engineering
KW  - Corynebacterium glutamicum
KW  - Targeted metabolomics
KW  - Metabolic flux analysis
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/26992
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-269920
SN  - 1475-2859
N1  - © 2012 Peifer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
VL  - 11
IS  - 138
PB  - BioMed Central
CY  - London
ER  -