Person: ARĞA, KAZIM YALÇIN
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ARĞA
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KAZIM YALÇIN
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Publication Metadata only The Stimulatory Effect of Mannitol on Levan Biosynthesis: Lessons from Metabolic Systems Analysis of Halomonas smyrnensis AAD6(T)(WILEY, 2013) TOKSOY ÖNER, EBRU; Ates, Ozlem; Arga, Kazim Y.; Oner, Ebru ToksoyHalomonas smyrnensis AAD(T) is a halophilic, gram-negative bacterium that can efficiently produce levan from sucrose as carbon source via levansucrase activity. However, systems-based approaches are required to further enhance its metabolic performance for industrial application. As an important step toward this goal, the genome-scale metabolic network of Chromohalobacter salexigens DSM3043, which is considered a model organism for halophilic bacteria, has been reconstructed based on its genome annotation, physiological information, and biochemical information. In the present work, the genome-scale metabolic network of C. salexigens was recruited, and refined via integration of the available biochemical, physiological, and phenotypic features of H. smyrnensis AAD6(T). The generic metabolic model, which comprises 1,393 metabolites and 1,108 reactions, was then systematically analyzed in silico using constraints-based simulations. To elucidate the relationship between levan biosynthesis and other metabolic processes, an enzyme-graph representation of the metabolic network and a graph decomposition technique were employed. Using the concept of control effective fluxes, significant links between several metabolic processes and levan biosynthesis were estimated. The major finding was the elucidation of the stimulatory effect of mannitol on levan biosynthesis, which was further verified experimentally via supplementation of mannitol to the fermentation medium. The optimal concentration of 30 g/L mannitol supplemented to the 50 g/L sucrose-based medium resulted in a twofold increase in levan production in parallel with increased sucrose hydrolysis rate, accumulated extracellular glucose, and decreased fructose uptake rate. (c) 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:1386-1397, 2013Publication Metadata only Genomic analysis of Brevibacillus thermoruber 423 reveals its biotechnological and industrial potential(SPRINGER, 2015) TOKSOY ÖNER, EBRU; Yildiz, Songul Yasar; Radchenkova, Nadja; Arga, Kazim Yalcin; Kambourova, Margarita; Oner, Ebru ToksoyBrevibacillus thermoruber 423 is a Gram-positive, motile, red-pigmented, spore-forming, aerobic, and thermophilic bacterium that is known to produce high levels of exopolysaccharide (EPS) with many potential uses in food, feed, cosmetics, and pharmaceutical and chemical industries. This bacterium not only is among the limited number of reported thermophilic EPS producers but also exceeds other thermophilic producers in light of the high level of polymer synthesis. By a systems-based approach, whole-genome analysis of this bacterium was performed to gain more insight about the biological mechanisms and whole-genome organization of thermophilic EPS producers and hence to develop rational strategies for the genetic and metabolic optimization of EPS production. Also with this study, the first genome analysis was performed on a thermophilic Brevibacillus species. Essential genes associated with EPS biosynthesis were detected by genome annotation, and together with experimental evidences, a hypothetical mechanism for EPS biosynthesis was generated. B. thermoruber 423 was found to have many potential applications in biotechnology and industry because of its capacity to utilize xylose and to produce EPS, isoprenoids, ethanol/butanol, lipases, proteases, cellulase, and glucoamylase enzymes as well as its resistance to arsenic.Publication Metadata only A novel levansucrase purified from halophilic bacteria halomonas smyrnensis AAD6T(2013-04-24) TURANLI, BESTE; ARĞA, KAZIM YALÇIN; TOKSOY ÖNER, EBRU; TURANLI B., ARĞA K. Y., TOKSOY ÖNER E.Publication Metadata only Effective stimulating factors for microbial levan production by Halomonas smyrnensis AAD6(T)(SOC BIOSCIENCE BIOENGINEERING JAPAN, 2015) TOKSOY ÖNER, EBRU; Sarilmiser, Hande Kazak; Ates, Ozlem; Ozdemir, Gonca; Arga, Kazim Yalcin; Oner, Ebru ToksoyLevan is a bioactive fructan polymer that is mainly associated with high-value applications where exceptionally high purity requirements call for well-defined cultivation conditions. In this study, microbial levan production by the halophilic extremophile Halomonas smyrnensis AAD6(T) was investigated systematically. For this, different feeding strategies in fed-batch cultures were employed and fermentation profiles of both shaking and bioreactor cultures were analyzed. Initial carbon and nitrogen source concentrations, production pH, NaCl and nitrogen pulses, nitrogen and phosphorous limitations, trace elements and thiamine contents of the basal production medium were found to affect the levan yields at different extends. Boric acid was found to be the most effective stimulator of levan production by increasing the sucrose utilization three-fold and levan production up to five-fold. This significant improvement implied the important role of quorum sensing phenomenon and its regulatory impact on levan production mechanism. Levan produced by bioreactor cultures under conditions optimized within this study was found to retain its chemical structure. Moreover, its biocompatibility was assessed for a broad concentration range. Hence H. smyrnensis AAD6(T) has been firmly established as an industrially important resource microorganism for high-quality levan production. (C) 2014, The Society for Biotechnology, Japan. All rights reserved.Publication Metadata only Genome-scale reconstruction of metabolic network for a halophilic extremophile, Chromohalobacter salexigens(ELSEVIER SCIENCE BV, 2009-09) TOKSOY ÖNER, EBRU; Ates, O.; Oner, E. Toksoy; Arga, K. Y.Publication Metadata only Identification of Exopolysaccharide Biosynthesis Mechanism of Halomonas smyrnensis AAD6(T)(ELSEVIER SCIENCE BV, 2012) TOKSOY ÖNER, EBRU; Sogutcu, Elif; Oner, Ebru Toksoy; Arga, Kazim YalcinPublication Metadata only The Genome-Based Metabolic Systems Engineering to Boost Levan Production in a Halophilic Bacterial Model(MARY ANN LIEBERT, INC, 2018) TOKSOY ÖNER, EBRU; Aydin, Busra; Ozer, Tugba; Oner, Ebru Toksoy; Arga, Kazim YalcinMetabolic systems engineering is being used to redirect microbial metabolism for the overproduction of chemicals of interest with the aim of transforming microbial hosts into cellular factories. In this study, a genome-based metabolic systems engineering approach was designed and performed to improve biopolymer biosynthesis capability of a moderately halophilic bacterium Halomonas smyrnensis AAD6(T) producing levan, which is a fructose homopolymer with many potential uses in various industries and medicine. For this purpose, the genome-scale metabolic model for AAD6(T) was used to characterize the metabolic resource allocation, specifically to design metabolic engineering strategies for engineered bacteria with enhanced levan production capability. Simulations were performed in silico to determine optimal gene knockout strategies to develop new strains with enhanced levan production capability. The majority of the gene knockout strategies emphasized the vital role of the fructose uptake mechanism, and pointed out the fructose-specific phosphotransferase system (PTSfru) as the most promising target for further metabolic engineering studies. Therefore, the PTSfru of AAD6(T) was restructured with insertional mutagenesis and triparental mating techniques to construct a novel, engineered H. smyrnensis strain, BMA14. Fermentation experiments were carried out to demonstrate the high efficiency of the mutant strain BMA14 in terms of final levan concentration, sucrose consumption rate, and sucrose conversion efficiency, when compared to the AAD6(T). The genome-based metabolic systems engineering approach presented in this study might be considered an efficient framework to redirect microbial metabolism for the overproduction of chemicals of interest, and the novel strain BMA14 might be considered a potential microbial cell factory for further studies aimed to design levan production processes with lower production costs.Publication Metadata only Identification of candidate genes related to ethanol tolerance in Saccharomyces cerevisiae via a systems based modular approach(ELSEVIER SCIENCE BV, 2012) TOKSOY ÖNER, EBRU; Kasavi, Ceyda; Arga, Kazim Yalcin; Oner, Ebru Toksoy; Kirdar, BetulPublication Metadata only Modeling of batch fermentation kinetics for levan production by Halomonas spp.(ELSEVIER SCIENCE BV, 2009-09) TOKSOY ÖNER, EBRU; Kazak, H.; Arga, K. Y.; Oner, E. Toksoy