Bioprocess

A bioprocess is a specific process that uses complete living cells or their components
(e.g., bacteria, enzymes, chloroplasts) to obtain desired products. This process is commonly
referred to as fermentation.

The very beginnings of fermentation technology, or as it is now better recognized, bioprocess

technology, were derived in part from the use of microorganisms for the production of foods
such as cheeses, yoghurts, sauerkraut, fermented pickles and sausages, soya sauce and other
Oriental products, and beverages such as beers, wines and derived spirits (Table 4.1).

The advantages of producing organic products by biological as opposed to purely chemical

methods are listed below -

Advantages

 Complex molecules such as proteins and antibodies cannot be produced by chemical

means

 Bioconversions give higher yields.

 Biological systems operate at lower temperatures, near neutral pH, etc.
 Much greater specificity of catalytic reaction.

Disadvantages

 Can be easily contaminated with foreign unwanted microorganisms, etc.

 The desired product will usually be present in a complex product mixture requiring
separation.
 Need to provide, handle and dispose of large volumes of water.
 Bioprocesses are usually extremely slow when compared with conventional chemical
processes
Range of Fermentation Processes

There are five major groups of commercially important fermentations -

 Those that produce microbial cells (biomass) as the product

 Those that produce microbial enzymes

 Those that produce microbial metabolites

 Those that produce recombinant products
 Those that modify a compound which is added to the fermentation – the transformation
process.
(1) Microbial Biomass

The commercial production of microbial biomass may be divided into two major processes.

 The production of yeast to be used in baking industry and

 The production of microbial cells to be used as human or animal food (single cell protein)

(2) Microbial enzymes

Microbial enzymes have the enormous advantage of being able to produced in large quantities by
established fermentation techniques. These are increasingly replacing conventional chemical
catalysts in many industrial processes. Examples include proteases, lipases, Carbohydrases etc.

(3) Microbial metabolites

There are two basic types of industrially important microbial metabolites.

 Primary metabolites
 Secondary metabolites

Many products of primary metabolism are considerable economic importance and are being
produced by fermentation. Ex. amino acids

Many secondary metabolites have antimicrobial activity, others are specific enzyme inhibitors and
many have pharmacological properties. Ex. antibiotics

(4) Recombinant products

The advent of recombinant DNA technology has extended the range of potential fermentation
products. Genes from higher organisms may be introduced into microbial cells such that the
recipients are capable of synthesizing foreign proteins. A wide range microbial cells have been used
as hosts for such systems including E.coli, Saccharomyces cerevisiae and filamentous fungi.

(5) Transformation processes

Microbial cells may be used to convert a compound into a structurally related, financially more
valuable compound e.g. steroid biotransformation.

Other products that can be obtained using fermentation include

  Biofuels (e.g. bioethanol, biobutanol, biodiesel)
 Biochemicals (3-hydroxypropionic acid and ethylene).
 Biopharmaceuticals (vaccines, interferons, growth factors hormones etc)

 Nutraceuticlas (Dietary supplement e.g. vitamin B supplement)

Upstream processing (USP) and Downstream processing (DSP)

Industrial fermentations comprise both upstream processing (USP) and downstream processing
(DSP). USP involves all factors and processes leading to, and including, the fermentation and
consists of three main areas.

The first includes selection of a microbial strain characterized by the ability to synthesize a specific
product having the desired commercial value. This strain then is subjected to improvement
protocols to maximize the ability of the strain to synthesize economical amounts of the product.

The second involves fermentation media, especially the selection of suitable cost-effective carbon
and energy sources, along with other essential nutrients. This media optimization is a vital aspect
of process development to ensure maximization of yield and profit.

The third is the fermentation itself, which is usually performed under rigorously controlled
conditions, developed to optimize the growth of the organism or the production of a target
microbial product.

DSP encompasses all processes following the fermentation. It has the primary aim of efficiently,
reproducibly and safely recovering the target product to the required specifications, while
maximizing recovery yield and minimizing costs. The target product may be recovered by
processing the cells or the spent medium depending upon whether it is an intracellular or
extracellular product. The level of purity that must be achieved is usually determined by the
specific use of the product.

Downstream Processing

A widely recognized heuristic for categorizing downstream processing operations divides them
into four groups which are applied in order to bring a product from its natural state as a
component of a tissue, cell or fermentation broth through progressive improvements in purity
and concentration.
1) Removal of insolubles is the first step and involves the capture of the product as a solute in a
particulate-free liquid, for example the separation of cells, cell debris or other particulate matter
from fermentation broth containing an antibiotic. Typical operations include
filtration, centrifugation, sedimentation, precipitation and flocculation. Additional operations
such as grinding, homogenization, or leaching, required to recover products from solid sources
such as plant and animal tissues, are usually included in this group.

2) Product isolation is the removal of those components whose properties vary markedly from
that of the desired product. For most products, water is the chief impurity and isolation steps are
designed to remove most of it, reducing the volume of material to be handled and concentrating
the product. Solvent extraction, adsorption, ultrafiltration and precipitation are some of the unit
operations involved.

3) Product purification is done to separate those contaminants that resemble the product very
closely in physical and chemical properties. Consequently steps in this stage are expensive to carry
out and require sensitive and sophisticated equipment. This stage contributes a significant fraction
of the entire downstream processing expenditure. Examples of operations include affinity, size
exclusion, reversed phase chromatography and crystallization

4) Product polishing describes the final processing steps which end with packaging of the product
in a form that is stable, easily transportable and convenient. Crystallization, desiccation and
drying (e.g. spray drying, freeze drying) are typical unit operations.