Optimal Process Synthesis for the Production of Multiple Recombinant Proteins

IRIBARREN, OSCAR ALBERTO; MONTAGNA, JORGE MARCELO; VECCHIETTI, ALDO R.; ANDREWS, BARBARA; ASENJO, JUAN; PINTO, JOSÉ M.

BIOTECHNOLOGY PROGRESS

American Chemical Society

Año: 2004 vol. 20 p. 1032 - 1043

8756-7938

This paper presents a novel solution strategy for the synthesis of multiproduct and multihost protein production processes. There are several possible hosts that may express each of the products, and different downstream processing separation and purification tasks are needed, which in part depend on the host selection. Moreover, alternative unit operations may be available for some of these separation tasks. Finally, these processing units may be arranged in different configurations. A single mixed-integer optimization model represents the different decisions involved in synthesizing a plant for producing multiple proteins. The mathematical model permits to make these decisions simultaneously, to optimize the profit of the multi product plant. An example is solved for a plant that must produce four proteins for which there are four hosts for their expression (Escherichia coli, mammalian cells of CHO, and yeast - that depending on the product may express it as an extra or intracellular protein) that require 15 stages with choices of unit operations as well as in or out of phase operations.