November 1-5, 2015
Carotenes such as β-carotene have a positive impact in human health as a precursor of vitamin A. Structural complexity of these compounds makes their chemical synthesis a difficult endeavor, facilitating the need for their biological production. Continuous operation can be used in these processes to allow for increased cell viability through the mitigation of substrate and product inhibition, thereby increasing the productivity of the carotenoid product. This work looks to examine the operating conditions necessary to achieve the maximum production of the desired carotenoid products when produced via continuous operation. First, a two-level parameter estimation method is utilized to develop a reliable kinetic model for the batch production of carotenoids via fermentation to describe the glucose consumption, metabolic product formation and depletion, and the carotenoid production in the Saccharomyces cerevisiae strain mutant SM14 with 20 g/L glucose as the carbon source. These models are then extended to the study of a novel continuous bioreactor system using a two feed configuration that gives the ability to use flowrate and glucose concentration of the feed stream as independent manipulated variables. Dynamic optimization techniques are then used to determine the optimal control actions governing the dilution rate and glucose concentration in order to maximize the carotenoid productivity during continuous operation. Finally, a model predictive control methodology utilizing state estimation via available online measurements and real time dynamic optimization is proposed to allow for the real-time control of this novel system.
Nazmul Karim, Jonathan Raftery, and Xinghua Pan, "Optimal control of a continuous bioreactor for maximized beta-carotene production" in "Integrated Continuous Biomanufacturing II", Chetan Goudar, Amgen Inc. Suzanne Farid, University College London Christopher Hwang, Genzyme-Sanofi Karol Lacki, Novo Nordisk Eds, ECI Symposium Series, (2015). http://dc.engconfintl.org/biomanufact_ii/100