Downstream Processing

The separation of bioactive compounds from crude fermentation broths or plant extracts requires a combination of traditional chemical engineering unit operations and those that are quite different. It is important to maintain the compound's bioactivity while maximizing its purity and yield. Two major problems to be addressed are that the compounds is usually present in very low concentrations, namely, a few hundred parts per million to 10% of the broth, and the impurities could have physicochemical properties that are similar to the desired compound, making conventional separations difficult.

The primary downstream operation is the removal of insolubles (e.g., by sedimentation, filtration, centrifugation, membranes), followed by isolation of the compound (e.g., precipitation, extraction, adsorption, membranes), final purification (e.g., crystallization, chromatography), and drying (conventional dryers or spray dryer). These unit operations will be discussed in Chapter 13.

Major unit operations involved in the downstream of manufacture of several fermentation processes are listed below:


downstream purification processes

Food stuff

filtration, separation, mixing, distillation, steriliza-

tion, drying


filtration, distillation

Amino acids,

cell separation, chromatographic purification, ex-


traction, crystallization

Citric acid

separation, precipitation, activated carbon purifi-


Lactic acid

filtration, decantation, vacuum evaporation, centri-



filtration, distillation

Vitamin B12

activated carbon treatment, extraction, ion ex-



pasteurization, precipitation, decantation, drying,

grinding grinding

Tetracycline filtration, precipitation, adsorption, crystallization, centrifugation, vacuum drying Bacitracin filtration, extraction, vacuum drying

Steroids extraction, crystallization

Bioprotein filtration, centrifugation, drying

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