TY  - JOUR
A1  - Basler, Georg
A1  - Grimbs, Sergio
A1  - Nikoloski, Zoran
T1  - Optimizing metabolic pathways by screening for feasible synthetic reactions
JF  - Biosystems : journal of biological and information processing sciences
N2  - Background: Reconstruction of genome-scale metabolic networks has resulted in models capable of reproducing experimentally observed biomass yield/growth rates and predicting the effect of alterations in metabolism for biotechnological applications. The existing studies rely on modifying the metabolic network of an investigated organism by removing or inserting reactions taken either from evolutionary similar organisms or from databases of biochemical reactions (e.g., KEGG). A potential disadvantage of these knowledge-driven approaches is that the result is biased towards known reactions, as such approaches do not account for the possibility of including novel enzymes, together with the reactions they catalyze.
 Results: Here, we explore the alternative of increasing biomass yield in three model organisms, namely Bacillus subtilis, Escherichia coil, and Hordeum vulgare, by applying small, chemically feasible network modifications. We use the predicted and experimentally confirmed growth rates of the wild-type networks as reference values and determine the effect of inserting mass-balanced, thermodynamically feasible reactions on predictions of growth rate by using flux balance analysis.
 Conclusions: While many replacements of existing reactions naturally lead to a decrease or complete loss of biomass production ability, in all three investigated organisms we find feasible modifications which facilitate a significant increase in this biological function. We focus on modifications with feasible chemical properties and a significant increase in biomass yield. The results demonstrate that small modifications are sufficient to substantially alter biomass yield in the three organisms. The method can be used to predict the effect of targeted modifications on the yield of any set of metabolites (e.g., ethanol), thus providing a computational framework for synthetic metabolic engineering.
KW  - Metabolic networks
KW  - Optimization
KW  - Mass-balanced reactions
KW  - Synthetic biology
Y1  - 2012
U6  - https://doi.org/10.1016/j.biosystems.2012.04.007
SN  - 0303-2647
VL  - 109
IS  - 2
SP  - 186
EP  - 191
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Larhlimi, Abdelhalim
A1  - Blachon, Sylvain
A1  - Selbig, Joachim
A1  - Nikoloski, Zoran
T1  - Robustness of metabolic networks a review of existing definitions
JF  - Biosystems : journal of biological and information processing sciences
N2  - Describing the determinants of robustness of biological systems has become one of the central questions in systems biology. Despite the increasing research efforts, it has proven difficult to arrive at a unifying definition for this important concept. We argue that this is due to the multifaceted nature of the concept of robustness and the possibility to formally capture it at different levels of systemic formalisms (e.g, topology and dynamic behavior). Here we provide a comprehensive review of the existing definitions of robustness pertaining to metabolic networks. As kinetic approaches have been excellently reviewed elsewhere, we focus on definitions of robustness proposed within graph-theoretic and constraint-based formalisms.
KW  - Robustness
KW  - Metabolic networks
KW  - Graph theory
KW  - Constraint-based approaches
Y1  - 2011
U6  - https://doi.org/10.1016/j.biosystems.2011.06.002
SN  - 0303-2647
VL  - 106
IS  - 1
SP  - 1
EP  - 8
PB  - Elsevier
CY  - Oxford
ER  -