@article {43047,
	title = {Exploring the differences in metabolic behavior of astrocyte and glioblastoma: a flux balance analysis approach},
	journal = {Systems and Synthetic Biology},
	volume = {9},
	year = {2015},
	month = {DEC},
	pages = {159-177},
	doi = {10.1007/s11693-015-9183-9},
	author = {Bhowmick, Rupa and Subramanian, Abhishek and Sarkar, Ram Rup}
}
@article {44119,
	title = {Exploring the role of GS-GOGAT cycle in microcystin synthesis and regulation - a model based analysis},
	journal = {Molecular Biosystems},
	volume = {13},
	year = {2017},
	month = {DEC},
	pages = {2603-2614},
	type = {Article},
	abstract = {Toxic 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.},
	doi = {10.1039/c7mb00342k},
	author = {Banerjee, Swarnendu and Subramanian, Abhishek and Chattopadhyay, Joydev and Sarkar, Ram Rup}
}
@article {45464,
	title = {Evolutionary perspectives of genotype-phenotype factors in leishmania metabolism},
	journal = {Journal of Molecular Evolution},
	volume = {86},
	year = {2018},
	month = {AUG},
	pages = {443-456},
	type = {Article},
	abstract = {<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>},
	keywords = {Codon usage, Evolutionary rate variation, Leishmania metabolism, Multi-functionality, Physiological fluxcoupling, Principal component regression (PCR)},
	issn = {0022-2844},
	doi = {10.1007/s00239-018-9857-5},
	author = {Subramanian, Abhishek and Sarkar, Ram Rup}
}
