Biochemical Product Recovery--First Steps

Why is product recovery challenging? Although most of the purification equipment for biotechnology is the same as that used throughout the chemical process industries, there are distinct differences.

Some tried-and-true chemical engineering unit processes and unit operations, e.g., adsorption and filtration, have been used routinely for years by biochemical engineers. Other steps are presently undergoing extensive research because they are needed for the difficult isolations of the exciting new protein products.

Dual goals: concentration and purification for the early steps in recovery that deal with dilute, impure materials.

Very large vessels are required when the solutions are so dilute. It is essential to reduce the amount of water.

An example is the solvent extraction of penicillin from acidified fermentation broth. The purity of penicillin at the end of fermentation may be a few per cent. Extraction into an immiscible solvent such as MIBK (methylisobutylketone) leaves behind the salts and polar organic molecules, e.g., sugars. In older processes, the ratio of MIBK to broth was about 1/5, and the distribution coefficient so favors penicillin that step yields were excellent. At this point the penicillin purity on a dry basis was already 70 to 80 per cent. Extraction back into water had a ratio of MIBK to water of 40/1, and the pH was between 7 and 8 where the distribution coefficient greatly favors water. The concentration factor increased by 5 times 40 or 200, and the purity was over 90 per cent. Modern penicillin fermentation achieves a concentration of roughly four per cent by weight of product in the broth, and the above ratios have been adjusted to suit the solubilities in organic solvent and water. It is relatively easy to crystallize a final, very pure product from concentrated aqueous solution.

Early purification by ion exchange has roughly similar performance. A large volume of broth is passed over the ion exchange resin, and the volume of eluant is relatively small. Again there is a highly favorable reduction in the volumes for subsequent handling and a significant increase in purity.
 Purification of proteins is much different. Click for an overview.


An excerpt from the text, BASIC Biochemical Engineering, by H.R. Bungay. Edited for the World Wide Web by Tammy A. Heesakker then later made into bullets in 1999.