Metabolic pathway analysis structural

Systems Analysis of Metabolic Pathways Network Structure Functional Network Inference Discussion... 

Another two key concepts in metabolic engineering are metabolic pathway analysis and metabolic pathway modeling. The former is used for assessing inherent network properties in the complete biochemical reaction networks. It involves identification of the metabolic network structure (or pathway topology), quantification of the fluxes through the branches of the metabolic network, and identification of the control structures within the metabolic network. 

Due to lack of kinetic parameters, structural metabolic network modeling has been widely applied for analyzing cellular metabolism under steady-state. Depending on what assumptions are made and whether experimental data are required, different techniques have been developed to analyze the invariant of metabohc networks such as metabolic flux analysis (MFA), flux balance analysis (FBA), and metabolic pathway analysis (MPA) including elementary mode and extreme pathway analyses (Lewis et al. 2012 Stephanopoulos et al. 1998 Trinh et al. 2(X)9). 

In this section, we describe a recently proposed approach that aims overcome some of the difficulties [23, 84, 296, 325] Structural Kinetic Modeling (SKM) seeks to provide a bridge between stoichiometric analysis and explicit kinetic models of metabolism and represents an intermediate step on the way from topological analysis to detailed kinetic models of metabolic pathways. Different from approximative kinetics described above, SKM is based on those properties that are a priori independent of the functional form of the rate equation. 

Phylogenic profiling Proteins that function together in a pathway or structural complex are likely to evolve together. Protein profile analysis for degree of match or similarity Function and structure linkages to other proteins that participate in a common structural complex or metabolic pathway [19]... 

The next phase in pathway analysis involves biochemical procedures. As many metabolic intermediates as possible are isolated, their structures are determined, the order of reactions is determined, and the enzymes that catalyze the different reaction steps are isolated and characterized. The mutants isolated for the complementation analysis are also... 

Further analysis of celery samples taken from the aforementioned study characterized 14 metabolites. These structures included simple hydroxy-x-triazines (GS-11526, GS-17794, GS-11957, GS-17791, GS-35713, and cyanuric acid), side-chain oxidized hydroxy-x-triazines (MCO-III-25 and MCO-IV-34), oxidized parent metabolites (GS-16141 and GS-16158), and dealkylated fiiiomethyl-x-triazines (GS-11354 and GS-26831). A metabolic pathway for prometryn in celery is illustrated in Figure 7.9. 

Based on the postulated common metabolic pathway involved in DOD and TOD formation by PR3, it was assumed that palmitoleic acid containing a singular C9 cis double bond (a common structural property shared by oleic and ricinoleic acids), could be utilized by PR3 to produce hydroxy fatty acid. Bae et al. (2007) reported that palmitoleic acid could be utilized as a substrate for the production of hydroxy fatty acid by PR3. Structural analysis of the major product produced from palmitoleic acid by PR3 confirmed that strain PR3 could introduce two hydroxyl groups on carbon 7 and 9 with shifted migration of 9-cis double bond into 8-tram configuration, resulting in the formation of 7,10-dihydroxy-8( )-hexadecenoic acid (DHD) (Fig. 31.3).The time course study of DHD production showed that DHD formation was time-dependently increased, and peaked at 72 h after the addition of palmitoleic acid as substrate. However, production yield of DHD (23%) from palmitoleic acid was relatively low when compared to that of DOD (70%) from oleic acid (Hou and Bagby, 1991). 

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