01008nas a2200157   4500008004100000245015600041210006900197260000800266520033300274100002500607700001900632700001900651700002800670700002100698856013100719       2018                        eng d00aEfforts to access the potent antitrypanosomal marine natural product janadolide: synthesis of des- tert -butyl janadolide and its biological evaluation0 aEfforts to access the potent antitrypanosomal marine natural pro  cFEB3 aTo identify novel antitrypanosomal agents based on Janadolide, a potent macrocyclic polyketide–peptide hybrid, a macrolactonization strategy was explored. We prepared des-tert-butyl Janadolide and evaluated its antitrypanosomal activity. Our findings suggest that the tert-butyl group is necessary for the desired bioactivity.1 aAthawale, Paresh, R.1 aJachak, Gorakh1 aShukla, Anurag1 aShanmugam, Dhanasekaran1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/efforts-access-potent-antitrypanosomal-marine-natural-product-janadolide-synthesis-des-tert01802nas a2200193   4500008004100000022001400041245010800055210006900163260000800232490000700240520109100247100002401338700002401362700002501386700002401411700002101435700002801456856012401484       2018                        eng d  a2045-232200aEvaluating antimalarial efficacy by tracking glycolysis in Plasmodium falciparum using NMR spectroscopy0 aEvaluating antimalarial efficacy by tracking glycolysis in Plasm  cDEC0 v 83 aGlucose is an essential nutrient for Plasmodium falciparum and robust glycolytic activity is indicative of viable parasites. Using NMR spectroscopy, we show that P. falciparum infected erythrocytes consume similar to 20 times more glucose, and trophozoites metabolize similar to 6 times more glucose than ring stage parasites. The glycolytic activity, and hence parasite viability, can be measured within a period of 2 h to 5 h, using this method. This facilitates antimalarial bioactivity screening on ring and trophozoite stage parasites, exclusively. We demonstrate this using potent and mechanistically distinct antimalarial compounds such as chloroquine, atovaquone, cladosporin, DDD107498 and artemisinin. Our findings indicate that ring stage parasites are inherently more tolerant to antimalarial inhibitors, a feature which may facilitate emergence of drug resistance. Thus, there is a need to discover novel antimalarial compounds, which are potent and fast acting against ring stage parasites. The NMR method reported here can facilitate the identification of such molecules.1 aShivapurkar, Rupali1 aHingamire, Tejashri1 aKulkarni, Akshay, S.1 aRajamohanan, P., R.1 aReddy, Srinivasa1 aShanmugam, Dhanasekaran  uhttps://library.ncl.res.in/content/evaluating-antimalarial-efficacy-tracking-glycolysis-plasmodium-falciparum-using-nmr03197nas a2200277   4500008004100000022001400041245015400055210006900209260000800278300001000286490000700296520225700303653001302560653002102573653001702594653000702611653002002618653000902638653001802647653003102665653002902696100001802725700002802743700001902771856012902790       2022                        eng d  a1096-717600aEngineering nucleotide sugar synthesis pathways for independent and simultaneous modulation of N-glycan galactosylation and fucosylation in CHO cells0 aEngineering nucleotide sugar synthesis pathways for independent   cNOV  a61-710 v743 a<p>
	Glycosylation of recombinant therapeutics like monoclonal antibodies (mAbs) is a critical quality attribute. N-glycans in mAbs are known to affect various effector functions, and thereby therapeutic use of such glycoproteins can depend on a particular glycoform profile to achieve desired efficacy. However, there are currently limited options for modulating the glycoform profile, which depend mainly on over-expression or knock-out of glyco-syltransferase enzymes that can introduce or eliminate specific glycans but do not allow predictable glycoform modulation over a range of values. In this study, we demonstrate the ability to predictably modulate the gly-coform profile of recombinant IgG. Using CRISPR/Cas9, we have engineered nucleotide sugar synthesis pathways in CHO cells expressing recombinant IgG for combinatorial modulation of galactosylation and fucosylation. Knocking out the enzymes UDP-galactose 4 `-epimerase (Gale) and GDP-L-fucose synthase (Fx) resulted in ablation of de novo synthesis of UDP-Gal and GDP-Fuc. With Gale knock-out, the array of N-glycans on recom-binantly expressed IgG is narrowed to agalactosylated glycans, mainly A2F glycan (89%). In the Gale and Fx double knock-out cell line, agalactosylated and afucosylated A2 glycan is predominant (88%). In the double knock-out cell line, galactosylation and fucosylation was entirely dependent on the salvage pathway, which allowed for modulation of UDP-Gal and GDP-Fuc synthesis and intracellular nucleotide sugar availability by controlling the availability of extracellular galactose and fucose. We demonstrate that the glycoform profile of recombinant IgG can be modulated from containing predominantly agalactosylated and afucosylated glycans to up to 42% and 96% galactosylation and fucosylation, respectively, by extracellular feeding of sugars in a dose-dependent manner. By simply varying the availability of extracellular galactose and/or fucose, galactosylation and fucosylation levels can be simultaneously and independently modulated. In addition to achieving the pro-duction of tailored glycoforms, this engineered CHO host platform can cater to the rapid synthesis of variably glycoengineered proteins for evaluation of biological activity.</p>
10aAntibody10aCell engineering10aFucosylation10aFx10aGalactosylation10aGale10aglycosylation10aNucleotide sugar synthesis10aRecombinant therapeutics1 aPrabhu, Anuja1 aShanmugam, Dhanasekaran1 aGadgil, Mugdha  uhttps://library.ncl.res.in/content/engineering-nucleotide-sugar-synthesis-pathways-independent-and-simultaneous-modulation-n02432nas a2200265   4500008004100000022001400041245011700055210006900172260000800241300001100249490000700260520150700267653001301774653002601787653001801813653002501831653002801856653002701884653002801911100002301939700002501962700002801987700002002015856013102035       2025                        eng d  a2211-926400aExpanding the Egbenema horizon: Novel species discovery in India and first complete genome assembly of the genus0 aExpanding the Egbenema horizon Novel species discovery in India   cAUG  a1042560 v903 a<p>
	The recognition of Egbenema bharatensis, a novel species of cyanobacteria from the Northern Western Ghats, extends the ecological and phylogenetic understanding of the genus Egbenema and highlights terrestrial microbial diversity of the region. Morphological characterization revealed resemblance with other Egbenema species but was inconclusive for definitive taxonomic classification. Preliminary phylogenetic analysis based on 16S rRNA gene sequences indicated affiliation with the genus but showed less than 98 % similarity to known species, pointing toward taxonomic distinctiveness. Analysis of the 16S-ITS region further supported this differentiation, revealing unique secondary structural features. Based on these findings, we propose the isolate as a novel species within Egbenema. Whole-genome sequencing provided full resolution and functional genome annotation revealed nitrogen fixation, cobalamin biosynthesis, and stress tolerance pathways, suggesting its metabolic versatility and potential biotechnological applications. The presence of multiple toxin-antitoxin systems also reflects its adaptability to environmental fluctuation. This study also presents the first complete genome of the genus Egbenema, filling a significant gap in cyanobacterial genomic resources. These findings encourage integrative taxonomic practices and affirm the significance of exploring biodiversity hotspots for uncovering cryptic microbial diversity with ecological and industrial potential.</p>
10a16S rRNA10aBiodiversity hotspots10aCyanobacteria10aEgbenema bharatensis10aITS secondary structure10aNorthern Western Ghats10awhole-genome sequencing1 aBhagat, Jayesh, M.1 aKhilari, Ajinkya, A.1 aShanmugam, Dhanasekaran1 aPatankar, Meena  uhttps://library.ncl.res.in/content/expanding-egbenema-horizon-novel-species-discovery-india-and-first-complete-genome-assembly