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Industrial Fermentation: Upstream and Downstream Process Overview - Malithi Weerakkody - 07-04-2013

Depending on the circumstance, the term fermentation can have three meanings. In a physiological sense, fermentation refers to a process that produces energy by breaking down of energy-rich compounds under anaerobic conditions. This is the basis of food fermentation, which is commonly used in the food industry in order to produce diverse food products and also as a food preservation method. In a biotechnological context though, this term is used in a much broader sense. There, fermentation means a process in which microorganisms that are cultured on a large-scale under aerobic or anaerobic conditions, convert a substrate into a product which is useful to man.

This article attempts to provide an overview of the industrial fermentation process, mainly focusing on various types of fermentations, the basic steps in a typical fermentation process and the major industrial applications of fermentation.

Basic Steps of Industrial Fermentation

Any industrial fermentation operation can be broken down into three main stages, viz, upstream processing, the fermentation process and downstream processing.

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Upstream processing includes formulation of the fermentation medium, sterilisation of air, fermentation medium and the fermenter, inoculum preparation and inoculation of the medium.

The fermentation medium should contain an energy source, a carbon source, a nitrogen source and micronutrients required for the growth of the microorganism along with water and oxygen, if necessary.

A medium which is used for a large scale fermentation, in order to ensure the sustainability of the operation, should have the following characteristics;
1. It should be cheap and easily available
2. It should maximise the growth of the microorganism, productivity and the rate of formation of the desired product
3. It should minimise the formation of undesired products

Usually, waste products from other industrial processes, such as molasses, lignocellulosic wastes, cheese whey and corn steep liquor, after modifying with the incorporation of additional nutrients, are used as the substrate for many industrial fermentations.

Sterilisation is essential for preventing the contamination with any undesired microorganisms. Air is sterilised by membrane filtration while the medium is usually heat sterilised. Any nutrient component which is heat labile is filter-sterilised and later added to the sterilised medium. The fermenter may be sterilised together with the medium or separately.

Inoculum build up is the preparation of the seed culture in amounts sufficient to be used in the large fermenter vessel. This involves growing the microorganisms obtained from the pure stock culture in several consecutive fermenters. This process cuts down the time required for the growth of microorganisms in the fermenter, thereby increasing the rate of productivity. Then the seed culture obtained through this process is used to inoculate the fermentation medium.

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Inoculum preparation procedure

The fermentation process involves the propagation of the microorganism and production of the desired product. The fermentation process can be categorised depending on various parameters.

It can be either aerobic fermentation, carried out in the presence of oxygen or anaerobic fermentation, carried out in the absence of oxygen. Many industrial fermentation are carried out under aerobic conditions where a few processes such as ethanol production by yeast require strictly anaerobic environments.

The fermentation process can also be divided into three basic systems, namely batch, continuous or fed-batch, depending on the feeding strategy of the culture and the medium into the fermenter. Each of these processes has their own advantages and disadvantages. In a batch operation, the medium and the culture are initially fed into the vessel and it is then closed. After that, no components are added apart from oxygen (in an aerobic process) and acid or alkali for the pH adjustment. The fermentation is allowed to run for a predetermined period of time and the product is harvested at the end. In a continuous process, fresh medium is continuously added and the products, along with the culture is removed at the same rate, thus maintaining constant concentrations of nutrients and cells are maintained throughout the process. A fed-batch system is a combination of these two systems where additional nutrients are added to the fermenter as the fermentation is in progress. This extends the time of operation but the products are harvested at the end of the production cycle as in a batch fermenter.

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The process can also be categorised as solid state fermentation (SSF) or submerged fermentation (SmF), depending on the amount of free water in the medium. In a solid state fermentation, the medium contains no free flowing water. The organisms are grown in a solid substrate which is moistened. This is used in certain industrial process such as ‘koji’ fermentation from soybeans, production of amylase and protease by Aspergillus oryzae on roasted soybeans and wheat, bioremediation, detoxification of agro-industrial wastes, etc. Submerged fermentation is in which microorganisms grow submerged in a liquid medium where free water is abundant. This is the method of choice for many industrial operations over SSF although SSF is also rapidly gaining interest in the present.

A comparison of SSF and SmF

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Downstream Processing includes the recovery of the products in a pure state and the effluent treatment. Product recovery is carried out through a series of operations including cell separation by settling, centrifugation or filtration; product recovery by disruption of cells (if the product is produced intracellularly); extraction and purification of the product. Finally, the effluents are treated by chemical, physical or biological methods.

Fermentation Products

Commercially important products of fermentation can be described in five major groups as follows.

1. Biomass (Baker’s yeast, SCP, Starter cultures, animal feed, etc.)
2. Primary metabolites (amino acids, organic acids, vitamins, polysaccharides, ethanol, etc.) and secondary metabolites (antibiotics, etc.)
3. Bioconvertion or biotransformation products (steroid biotransformation, L-sorbitol etc.)
4. Enzymes (amylase, lipase, cellulase, etc.)
5. Recombinant products (some vaccines, hormones such as isulin and growth hormones etc.)


1. Food Biotechnology (2nd edition) edited by Kalidas Shetty, Gopinadhan Paliyath, Anthony Pometto and Robert E. Levin

2. Introduction to Biochemical Engineering By Dubasi Govardhana Rao