02095nas a2200241 4500008004100000022001400041245016200055210006900217260009500286300001200381490000800393520114900401653002001550653002101570653002101591653001501612653001301627653001901640653002401659100002601683700002101709856012301730 2015 eng d a0888-754300aComparison of codon usage bias across leishmania and trypanosomatids to understand mRNA secondary structure, relative protein abundance and pathway functions0 aComparison of codon usage bias across leishmania and trypanosoma a525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USAbACADEMIC PRESS INC ELSEVIER SCIENCEcOCT a232-2410 v1063 a

Understanding the variations in gene organization and its effect on the phenotype across different Leishmania species, and to study differential clinical manifestations of parasite within the host, we performed large scale analysis of codon usage patterns between Leishmania and other known Trypanosomatid species. We present; the causes and consequences of codon usage bias in Leishmania genomes with respect to mutational pressure, translational selection and amino acid composition bias. We establish GC bias at wobble position that governs codon usage bias across Leishmania species, rather than amino acid composition bias. We found that, within Leishmania, homogenous codon context coding for less frequent amino acid pairs and codons avoiding formation of folding structures in mRNA are essentially chosen. We predicted putative differences in global expression between genes belonging to specific pathways across Leishmania. This explains the role of evolution in shaping the otherwise conserved genome to demonstrate species-specific function-level differences for efficient survival. (C) 2015 Elsevier Inc. All rights reserved.

10aAmino acid bias10aBase composition10aCodon usage bias10aLeishmania10aMutation10aSelection bias10aSpecies specificity1 aSubramanian, Abhishek1 aSarkar, Ram, Rup uhttps://library.ncl.res.in/content/comparison-codon-usage-bias-across-leishmania-and-trypanosomatids-understand-mrna-002536nas a2200205 4500008004100000022001400041245012100055210006900176260000800245520178100253653002102034653003402055653001302089653002402102653001502126100001802141700002202159700002102181856012802202 2019 eng d a0887-358500aMolecular basis of drug resistance in smoothened receptor: an in silico study of protein resistivity and specificity0 aMolecular basis of drug resistance in smoothened receptor an in  cOCT3 a

Smoothened (SMO) antagonist Vismodegib effectively inhibits the Hedgehog pathway in proliferating cancer cells. In early stage of treatment, Vismodegib exhibited promising outcomes to regress the tumors cells, but ultimately relapsed due to the drug resistive mutations in SMO mostly occurring before (primary mutations G497W) or after (acquired mutations D473H/Y) anti-SMO therapy. This study investigates the unprecedented insights of structural and functional mechanism hindering the binding of Vismodegib with sensitive and resistant mutant variants of SMO (SMOMut). Along with the basic dynamic understanding of Vismodegib-SMO complexes, network propagation theory based on heat diffusion principles is first time applied here to identify the modules of residues influenced by the individual mutations. The allosteric modulation by GLY497 residue in Vismodegib bound SMO wild-type (SMOWT) conformation depicts the interconnections of intermediate residues of SMO with the atom of Vismodegib and identify two important motifs (E-X-P-L) and (Q-A-N-V-T-I-G) mediating this allosteric regulation. In this study a novel computational framework based on the heat diffusion principle is also developed, which identify significant residues of allosteric site causing drug resistivity in SMOMut. This framework could also be useful for assessing the potential allosteric sites of different other proteins. Moreover, previously reported novel inhibitor ``ZINC12368305,'' which is proven to make an energetically favorable complex with SMOWT is chosen as a control sample to assess the impact of receptor mutation on its binding and subsequently identify the important factors that govern binding disparity between Vismodegib and ZINC12368305 bound SMOWT/Mut conformations.

10aallosteric sites10amolecular dynamics simulation10aMutation10asmoothened receptor10aVismodegib1 aSinha, Noopur1 aChowdhury, Saikat1 aSarkar, Ram, Rup uhttps://library.ncl.res.in/content/molecular-basis-drug-resistance-smoothened-receptor-silico-study-protein-resistivity-and02655nas a2200241 4500008004100000022001400041245013500055210006900190260000800259300001200267490000700279520182500286653001502111653001702126653002402143653001302167653001702180653002302197100002202220700002302242700002302265856012502288 2024 eng d a1139-670900aStrain improvement for enhanced erythritol production by Moniliella pollinis Mutant-58 using jaggery as a cost-effective substrate0 aStrain improvement for enhanced erythritol production by Monilie cAPR a581-5960 v273 a

Erythritol has been produced by various microorganisms including Yarrowia, Moniliella, Aureobasidium, and Candida strains. Due to its relatively high price, erythritol sweetener is used lesser than other polyols despite having many advantages. Therefore, in this study, Moniliella pollinis strain was improved for erythritol production by chemical mutagenesis and subsequently screening for cost-effective carbon sources for the enhanced erythritol yield. M. pollinis was subjected to N-methyl N-nitro N-nitroso guanidine (NTG), ethyl methyl sulfonate (EMS), and UV mutagenesis for improved erythritol production. The fmutant strains were evaluated for enhanced erythritol production medium optimization by using different carbon substrates at the shake flask level. To enhance the production of erythritol and statistical media, optimization was carried out using a central composite design (CCD). Among 198 isolated mutants, Mutant-58 strain generated by EMS mutagenesis was selected for further assessment. The Mutant-58 strain showed significant morphological changes as compared to the parent strain. Furthermore, statistically optimized media composition resulted in the higher production of erythritol (91.2 & PLUSMN; 3.4 g/L) with a yield of 40.7 & PLUSMN; 3.4 % in shake flask experiments. The optimized medium composition for erythritol production constitutes (g/L) 225 jaggery, 4.4 yeast extract (YE), 4.4 KH2PO4, 0.31 MgSO4, and pH 5.5. The present study demonstrated strain improvement, media, and process optimization resulting in a 30% increase in the erythritol production in the Mutant-58 as compared to the parent strain. This is also the first instance where jaggery has been used as a cost-effective carbon source alternative to glucose for industrial-scale erythritol production.

10aErythritol10aFermentation10aMoniliella pollinis10aMutation10aOptimization10arenewable resource1 aKhatape, Anil, B.1 aRangaswamy, Vidhya1 aDastager, Syed, G. uhttps://library.ncl.res.in/content/strain-improvement-enhanced-erythritol-production-moniliella-pollinis-mutant-58-using