00592nas a2200145   4500008004100000245011600041210006900157260000800226300001200234490000600246100001900252700002600271700002100297856012800318       2015                        eng d00aExploring the differences in metabolic behavior of astrocyte and glioblastoma: a flux balance analysis approach0 aExploring the differences in metabolic behavior of astrocyte and  cDEC  a159-1770 v91 aBhowmick, Rupa1 aSubramanian, Abhishek1 aSarkar, Ram, Rup  uhttp://library.ncl.res.in/content/exploring-differences-metabolic-behavior-astrocyte-and-glioblastoma-flux-balance-analysis02140nas a2200169   4500008004100000245010600041210006900147260000800216300001400224490000700238520150200245100002401747700002601771700002601797700002101823856012601844       2017                        eng d00aExploring the role of GS-GOGAT cycle in microcystin synthesis and regulation - a model based analysis0 aExploring the role of GSGOGAT cycle in microcystin synthesis and  cDEC  a2603-26140 v133 aToxic cyanobacteria blooms populate water bodies by consuming external nutrients and releasing cyanotoxins that are detrimental for other aquatic species, producing a significant impact on the plankton ecosystem and food web. To exercise population-level control of toxin production, understanding the biochemical mechanisms that explain cyanotoxin regulation within a bacterial cell is of utmost importance. In this study, we explore the mechanistic events to investigate the dependence of toxin microcystin on external nitrogen, a known regulator of the toxin, and for the first time, propose a kinetic model that analyzes the intracellular conditions required to ensure nitrogen dependence on microcystin. We hypothesize that the GS-GOGAT cycle is manipulated by variable influx of different intracellular metabolites that can either disturb or promote the balance between the enzyme microcystin synthetase and substrate glutamate to produce variable microcystin levels. As opposed to the popular notion that nitrogen starvation increases microcystin synthesis, our analyses suggest that under certain intracellular metabolite regimes, this relationship can either be completely lost or reversed. External nitrogen can only complement the conditions fixed by intracellular glutamate, glutamine and 2-oxoglutarate. This mechanistic understanding can provide an experimentally testable hypothesis for exploring the less-known biology of microcystin synthesis and designing specific interventions.1 aBanerjee, Swarnendu1 aSubramanian, Abhishek1 aChattopadhyay, Joydev1 aSarkar, Ram, Rup  uhttp://library.ncl.res.in/content/exploring-role-gs-gogat-cycle-microcystin-synthesis-and-regulation-model-based-analysis02718nas a2200229   4500008004100000022001400041245008500055210006900140260000800209300001200217490000700229520192200236653001602158653003202174653002602206653002402232653003102256653004102287100002602328700002102354856011302375       2018                        eng d  a0022-284400aEvolutionary perspectives of genotype-phenotype factors in leishmania metabolism0 aEvolutionary perspectives of genotypephenotype factors in leishm  cAUG  a443-4560 v863 a<p>The sandfly midgut and the human macrophage phagolysosome provide antagonistic metabolic niches for the endoparasite Leishmania to survive and populate. Although these environments fluctuate across developmental stages, the relative changes in both these environments across parasite generations might remain gradual. Such environmental restrictions might endow parasite metabolism with a choice of specific genotypic and phenotypic factors that can constrain enzyme evolution for successful adaptation to the host. With respect to the available cellular information for Leishmania species, for the first time, we measure the relative contribution of eight inter-correlated predictors related to codon usage, GC content, gene expression, gene length, multi-functionality, and flux-coupling potential of an enzyme on the evolutionary rates of singleton metabolic genes and further compare their effects across three Leishmania species. Our analysis reveals that codon adaptation, multi-functionality, and flux-coupling potential of an enzyme are independent contributors of enzyme evolutionary rates, which can together explain a large variation in enzyme evolutionary rates across species. We also hypothesize that a species-specific occurrence of duplicated genes in novel subcellular locations can create new flux routes through certain singleton flux-coupled enzymes, thereby constraining their evolution. A cross-species comparison revealed both common and species-specific genes whose evolutionary divergence was constrained by multiple independent factors. Out of these, previously known pharmacological targets and virulence factors in Leishmania were identified, suggesting their evolutionary reasons for being important survival factors to the parasite. All these results provide a fundamental understanding of the factors underlying adaptive strategies of the parasite, which can be further targeted.</p>10aCodon usage10aEvolutionary rate variation10aLeishmania metabolism10aMulti-functionality10aPhysiological fluxcoupling10aPrincipal component regression (PCR)1 aSubramanian, Abhishek1 aSarkar, Ram, Rup  uhttp://library.ncl.res.in/content/evolutionary-perspectives-genotype-phenotype-factors-leishmania-metabolism