02344nas a2200241   4500008004100000022001400041245016400055210006900219260007100288300001200359490000700371520145300378653000801831653001301839653001401852653001201866653001801878653002401896653001401920100001801934700001901952856013101971       2015                        eng d  a8756-793800aManganese increases high mannose glycoform on monoclonal antibody expressed in cho when glucose is absent or limiting: implications for use of alternate sugars0 aManganese increases high mannose glycoform on monoclonal antibod  a111 RIVER ST, HOBOKEN 07030-5774, NJ USAbWILEY-BLACKWELLcMAR-APR  a460-4670 v313 a<p>Alternate sugars such as galactose and fructose are metabolized at a slower rate than glucose and result in lower accumulation of lactate. While low lactate accumulation is desirable, we report that complete substitution of glucose with these sugars results in an increase in M5 high mannose glycans. Surprisingly, this increase is much higher when the culture is supplemented with manganese: for example, when cells are cultured with galactose, M5 high mannose glycan content increased from 5% at 1 nM Mn2+ in the basal medium to 32% with 16 mu M Mn2+ supplementation. When galactose is supplemented with glucose maintained at low concentrations, a small reduction in high mannose glycans is seen. In control cultures with glucose, the high mannose content was however &lt;2% in this range of Mn2+ concentration. By varying Mn2+ and glucose supplementation levels, with or without galactose, we systematically demonstrate that Mn2+ concentration and glucose availability, together, significantly affect the high mannose glycan content. To our knowledge, this is the first report that shows that the effect of Mn2+ on high mannose glycan content depends on glucose availability. At each Mn2+ supplementation level evaluated, galactosylation percentages were highest for cultures where galactose was supplemented with glucose at non-limiting concentration. (c) 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:460-467, 2015</p>10aCHO10afructose10agalactose10aglucose10aglycosylation10ahigh-mannose glycan10amanganese1 aSurve, Tanaya1 aGadgil, Mugdha  uhttps://library.ncl.res.in/content/manganese-increases-high-mannose-glycoform-monoclonal-antibody-expressed-cho-when-glucose-002195nas a2200229   4500008004100000022001400041245010600055210006900161260000800230300001000238490000800248520141500256653002501671653001301696653001401709653002301723653002601746100002001772700001901792700002301811856013101834       2022                        eng d  a0168-165600aMathematical model of the multi-amino acid multi-transporter system predicts uptake flux in CHO cells0 aMathematical model of the multiamino acid multitransporter syste  cJAN  a40-490 v3443 aSupply and uptake of amino acids is of great importance to mammalian cell culture processes. Mammalian cells such as Chinese hamster ovary (CHO) cells express several amino acid (AA) transporters including uniporters and exchangers. Each transporter transports multiple AAs, making prediction of the effect of changed medium composition or transporter levels on individual AA transport rate challenging. A general kinetic model for such combinatorial amino acid transport, and a simplified analytical expression for the uptake rate as a function of amino acid concentrations and transporter levels is presented. From this general model, a CHO cell-specific AA transport model, to our knowledge the first such network model for any cell type, is constructed. The model is validated by its prediction of reported uptake flux and dependencies from experiments that were not used in model construction or parameter estimation. The model defines theoretical conditions for synergistic/repressive effect on the uptake rates of other AAs upon external addition of one AA. The ability of the CHO-specific model to predict amino acid interdependencies experimentally observed in other mammalian cell types suggests its robustness. This model will help formulate testable hypotheses of the effect of process changes on AA initial uptake, and serve as the AA transport component of kinetic models for cellular metabolism.10aAmino acid transport10aCHO cell10aExchanger10amathematical model10aMultiple transporters1 aSreejan, Ashley1 aGadgil, Mugdha1 aGadgil, Chetan, J.  uhttps://library.ncl.res.in/content/mathematical-model-multi-amino-acid-multi-transporter-system-predicts-uptake-flux-cho-cells