Metabolic regime control for production of Biotherapeutics in E. coli
Jashwant Kumar (Prof. Anurag Rathore and Prof. James Gomes)
12th July 2017, Wednesday, 04:30‐05:00 pm (25+5 mins), ChE Seminar hall
Bioprocessing relies on the harnessing of biological systems such as microbial, yeast, insect and mammalian cells to produce a desired product. Among microbial hosts, E. coli, a gramnegative bacterium, is one of the most widely used system for the production of biotherapeutics. Ranibizumab is a biotherapeutic expressed in E. coli, used to treat macular degeneration and macular oedema in elderly people. Inspite of advancement in bioprocess technology, the drug is still prohibitively expensive and beyond the reach of major sections of the society. It has been reported that the major cause of this hike in the cost of the drug is due to its low levels of expression and insufficient production. Lower production efficiency and high production cost of protein drugs are the major challenges of recombinant protein production. Hence, to achieve higher process efficiency and reproducibility, application of Metabolic regime control for production of Biotherapeutics in E. coli Study of Electrochemical Reduction of Carbon Dioxide ChE Graduat e Seminar Series Departmental Seminars Presented by Ph.D. Students ChE Graduat e Seminar Series Departmental Seminars Presented by Ph.D. Students advance control strategy is necessary. The control of biological system has been in general defined based on process variable measurements that characterize the condition of the reactor. It is perceived that by controlling the reactor conditions, the cell would synthesize a desired product in concentrations close to that predicted by process optimization or predetermined process trajectories. The models developed for such purposes are usually unable to capture the complex network of reactions and their regulation, and hence unable to exploit the full potential of the microorganism. This “gap” of the control design arises due to several reasons including the fact that certain advanced design methods get unwieldy when the number of state variables are more than 5 or 6. Since, no single controller design methodology can address all the problems in bioprocesses, we propose the development of two-tiered control system that computes the necessary control action for maintaining reactor conditions and while accounting for acceptable metabolic changes.