From Cellular Function to Industrial Products
2.1.6 Secreted Proteins
Many microorganisms secrete hydrolytic enzymes that degrade macromolecules to monomers that
may serve as carbon, energy and nitrogen sources. Among the most frequently secreted enzymes
are proteases (degradation of proteins), peptidases (degradation of peptides), amylases (degradation
of starch), xylanases (degradation of xylans), cellulases (degradation of cellulose). Through the
secretion of enzymes some microorganisms may grow on very complex nutrients, and the ability
for microorganisms to decompose leaves and other plant materials plays a very important role in
the overall carbon cycle. The ability of microorganisms to secrete enzymes has been exploited for
many generations, particularly in the food and feed industry. Thus, the use of
Aspergillus oryzae,
which is an efficient producer of the starch degrading enzymes a -amylase and glucoamylase, in the
koji-sauce production has been practiced for more than a thousand years. Furthermore, the secretion
of proteases and peptidases by lactic acid bacteria plays a very important role in many dairy
processes, both because the hydrolysis of proteins and peptides ensures supply of carbon and
energy sources that may be converted to acids and other flavors and because hydrolysis of many
peptides are important for proper flavor development. Today, enzymes are also used in detergents
to improve the washing process and in many different industrial processes, e.g., in the treatment of
cotton (see e.g. www.novo
7 for more details on the industrial application of enzymes).
Many of these industrial enzymes are today produced using a few host cells where genes encoding
the enzymes are introduced by genetic engineering.
The possibility to introduce foreign genes into a microbial host by genetic engineering and
hereby produce a specific protein in high amounts also paved the way for a completely new route
for production of pharmaceutical proteins like human growth hormone (hGH) and human insulin.
The first products (human insulin and hGH) were produced in recombinant
E. coli,
but soon
followed the exploitation of other expression systems like 5.
(introduced for
production of human insulin), insect cells, and mammalian cells (Chinese hamster ovary cells
and hybridoma cells). Today there are more than 55 protein drugs, largely recombinant proteins
and monoclonal antibodies that are often referred to as biotech drugs, and the top selling drugs
produce revenues of billions of US$. The biochemical processes underlying the synthesis of a
heterologous protein in a given host cell may be quite complex as many post-translational
modifications may take place and the secretory pathway may involve many individual steps.
Many of these processes are specific for the host system and it is therefore not possible to give a
short overview of the subject.
2.2 Biotech Processes - An Overview
When a microorganism or cell type has been identified to produce an interesting compound there
are a number of considerations to be made before an economically viable, industrial process can
be realized. In companies with a solid experience in design and scale-up of fermentation
processes there can be a relatively fast implementation of a new process, but still there are many
hurdles on the road to an efficient industrial process. Development of a fermentation process can
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