These organisms use diverse biochemical mechanisms, such as Kodam

These organisms use diverse biochemical mechanisms, such as Kodama and 4S pathways, to metabolize various polyaromatic sulfur heterocycles (PASHs). Of these, R. erythropolis IGTS8 was the first to be isolated for its ability to specifically cleave the C–S bond in PASHs without affecting the C–C bond (Kilbane & Jackowski, 1992). Since then, several Rhodococcus strains INCB024360 clinical trial have been studied (Izumi et al., 1994; Li et al., 1996; Ohshiro et al., 1996; Honda et al., 1998; Davoodi-Dehaghani et al., 2010) for specifically desulfurizing DBT and its derivatives via the 4S pathway. The desulfurization rates exhibited by

the wild-type bacteria are too low for commercialization (Kilbane, 2006). Despite numerous experimental efforts including genetic manipulations, desirable desulfurization rates are yet to be attained. From our study, it seems that this may be due to the fact that most of these studies have solely targeted the 4S pathways and desulfurizing (dsz) genes. Because the cellular phenotypes are the manifestations check details of complex interactions among various gene products and environmental factors, a systems biology

approach is critical for studying desulfurization. A comprehensive modeling approach can complement the existing and future experimental studies considerably. Such an approach would facilitate a more quantitative and insightful understanding of the interdependencies among the various pathways and associated reactions that largely determine the metabolic fluxes within

a desulfurizing strain, and hence its desulfurization activity. The resulting knowledge can then guide the design of environment and re-engineering of strains for enhancing desulfurization via the 4S pathway. This work represents the first attempt, to our knowledge, at reconstructing a stoichiometric model for the sulfur metabolism in R. erythropolis. It comprises a network of reaction Adenosine pathways involved in sulfur and central metabolism, and quantitatively describes the assimilation of sulfur from different sources into various biomass precursors. It successfully predicts two independent cell growth data and several phenotypes reported in the literature such as the effects of sulfate and various carbon sources on biodesulfurization activity. We have successfully used the model to compare the effects of eight carbon sources (citrate, ethanol, fructose, gluconate, glucose, glutamate, glycerol, and lactate) on desulfurizing activity and cell growth. The flux-based models have been widely used to study the metabolic networks of various microorganisms in a holistic manner (Burgard & Maranas, 2003; Suthers et al., 2009; Orth et al., 2010; Thiele & Palsson, 2010). Such a model for an organism is built on the known and hypothesized reactions that may take place within the organism (Gonzalez et al., 2008) based on its genomic, biochemical, and physiological information (Park et al., 2009).

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