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Lakshmanan, Meiyappan,Zhang, Zhaoyang,Mohanty, Bijayalaxmi,Kwon, Jun-Young,Choi, Hong-Yeol,Nam, Hyung-Jin,Kim, Dong-Il,Lee, Dong-Yup American Society of Plant Biologists 2013 PLANT PHYSIOLOGY - Vol.162 No.4
<P><I>A metabolic/regulatory network of rice incorporates two important tissue types, germinating seeds and photorespiring leaves, is validated through experiments with rice suspension cultures, and applied to analyze metabolic capability under flooding and drought conditions.</I></P>
Ang, Kok Siong,Lakshmanan, Meiyappan,Lee, Na-Rae,Lee, Dong-Yup Bentham Science Publishers 2018 Current genomics Vol.19 No.8
<P>In nature, microbes do not exist in isolation but co-exist in a variety of ecological and biological environments and on various host organisms. Due to their close proximity, these microbes interact among themselves, and also with the hosts in both positive and negative manners. Moreover, these interactions may modulate dynamically upon external stimulus as well as internal community changes. This demands systematic techniques such as mathematical modeling to understand the intrinsic community behavior. Here, we reviewed various approaches for metabolic modeling of microbial communities. If detailed species-specific information is available, segregated models of individual organisms can be constructed and connected via metabolite exchanges; otherwise, the community may be represented as a lumped network of metabolic reactions. The constructed models can then be simulated to help fill knowledge gaps, and generate testable hypotheses for designing new experiments. More importantly, such community models have been developed to study microbial interactions in various niches such as host microbiome, biogeochemical and bioremediation, waste water treatment and synthetic consortia. As such, the metabolic modeling efforts have allowed us to gain new insights into the natural and synthetic microbial communities, and design interventions to achieve specific goals. Finally, potential directions for future development in metabolic modeling of microbial communities were also discussed.</P>
Towards next generation CHO cell line development and engineering by systems approaches
Hong, Jong Kwang,Lakshmanan, Meiyappan,Goudar, Chetan,Lee, Dong-Yup Elsevier 2018 Current opinion in chemical engineering Vol.22 No.-
<P>Chinese hamster ovary (CHO) cells are the most prevalent mammalian cell factories for producing therapeutic biologics, due to its capacity for complex post-translational modifications, ability to grow well in suspension cultures and low susceptibility to human viral infections. Significant advances in various modules of the CHO cell line development and engineering (CLD&E) have contributed to up to 100-fold increase in the product yields over the last three decades. Although production yield still remains the major focus in CLD&E, product quality and long-term stability have increasingly appeared to be the additional criteria. Towards achieving such goals, various platforms involving high-throughput clonal evaluation in automated manner, efficient vector designs, RNA interference methods and genome editing techniques have been developed to generate highly productive clones much faster with desired quality attributes and cell line traits. Since CHO genome was sequenced, we can now systematically characterize CHO cells using high-throughput omics profiles and <I>in silico</I> computational models, thereby identifying relevant targets for rational cell engineering which can be readily validated by the emerging genome editing techniques in a targeted and precise manner. In this review, we summarize the history of CHO CLD&E, and then describe the major technological advancements along with the application areas. Lastly, our perspectives on the next generation CLD&E are provided within the context of mammalian systems biotechnology.</P>
Comparative phenotypic analysis of CHO clones and culture media for lactate shift
Hong, Jong Kwang,Nargund, Shilpa,Lakshmanan, Meiyappan,Kyriakopoulos, Sarantos,Kim, Do Yun,Ang, Kok Siong,Leong, Dawn,Yang, Yuansheng,Lee, Dong-Yup Elsevier 2018 Journal of biotechnology Vol.283 No.-
<P><B>Abstract</B></P> <P>We explored the effects of media and clonal variation on the lactate shift which can be considered as one of the desirable features in CHO cell culture. Various culture profiles with the specific growth and antibody production rates under three different media conditions in two CHO producing clones were evaluated by resorting to multivariate statistical analysis. In most cases, glutamine depletion coincided with lactate consumption, suggesting that glutaminolysis rather than glycolysis was the preferred pathway for the pyruvate supply toward lactate production. With respect to the lactate shift, high performing medium showed higher glutamate uptake, higher aspartate secretion and lower serine uptake compared to other media conditions. In addition, clone itself exhibited the desired lactate consumption more consistently accompanying with distinguishing phenotype. The clone exhibiting lactate shift produced lesser lactate in exponential phase but two-fold higher non-toxic alanine, thus leading to better culture environment. Thus, we understand the balanced selection of clone and media composition enables cells to utilize the metabolic pathways for the desired lactate shift.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Explored the effects of media and clonal variation on the lactate shift in CHO cells. </LI> <LI> Conducted multivariate statistical analysis of various CHO cell cultures. </LI> <LI> Found glutaminolysis as preferred pathway for lactate production by pyruvate supply. </LI> <LI> Understood the balanced selection of clone and media composition for lactate shift. </LI> </UL> </P>