Definition of Industrial Biotechnology

Industrial biotechnology is a set of practices that use living cells (such as bacteria, yeast, algae) or component of cells like enzymes, to generate industrial products and processes.

History

The baker‘s yeast „saccharomyces cerevisiae“ plays an important role in industrial fermentation processes. Baker‘s yeast is the first higher genome that was fully decoded in 1996 and contains 6000 genes. The genome database of baker‘s yeast is one of the most comprehensive and probably the best documented.
In the ancient fermentation process with yeast for beer production, sugar is decomposed to alcohol and carbonic acid. The process takes place via a plurality of intermediate steps and molecules. If the yeast gene is changed, the process is interrupted and an intermediate is formed. The applied genetic engineering determines the extent of the changes and it is possible to initiate completely new biochemical processes and thus create new molecules. The nature and yield of these molecules are controlled by genetic engineering.

But why is Industrial Biotechnology first now in the spotlight?

The tremendous progress in biology over the past years from the elucidation of the structure of DNA to today’s astonishing, rapid progress in the field of synthetic biology has positioned Industrial Biotech for the new round of innovation in chemical production. What in the past has lasted years with huge input of researchers and manual labs can today be achieved by using cutting-edge DNA-technology, robotics and AI, within months or weeks at a fraction of the cost. The typical process for engineering a new molecule involves four highly specialized and interdependent disciplines and is called DBTL-cycle.

• Computer-aided design and artificial intelligence to design the desired molecule
• Genome editing tools like CRISPR/Cas9 to build the designed molecule
• Robotic-tools and machine learning for cultivating the strains and to test to what extent the desired molecule was reached
• Machine Learning and artificial intelligence to analyze the results, learn how the parameters have affected the result and take decisions for new parameters in the next cycles.

The results are automatically stored in databases and are immediately compared with the results of other cycles and other research projects around the world and with references from the literature. The quality and depth of this database is a decisive factor for the success of a company in industrial biotechnology. The science in Industrial Biotechnology has evolved from an empirical trial & error approach to an systematic engineering science where, with high probability, the results in a new cycle are predictable based on data from the databases.

In the past and without the help of today’s technical achievements a single turn of a DBTL-cycle took months of work and to get the desired molecule several years. Cutting-edge DNA-technology, robotics and AI diminish the time down to weeks or soon days. The workflow of a DBTL cycle remains the same, but today it is possible to execute hundreds of strains parallel and simultaneously.

Safety

But what about safety? The genetic engineering applied should not be confused with the controversial gene manipulation since no genetically manipulated molecules are released. The gen-edited yeast is only a converter (process aid) and no genetically manipulated fragments can be detected in the desired end product. Like in a catalytic process the catalyst (yeast) is not in the final product.


No residual DNA or protein is presented in the final product. Centuries of experience in brewing and baking processes have shown that the use of yeast is safe, and no negative incidents have been documented in all these years. The advantage of using baker‘s yeast in the fermentation process is that it is easy to grow in the laboratory as well as in the industrial bioreactor and the results are identical.

Industrial Biotechnology = Simple and cost-effective production

A major advantage of industrial biotechnology compared to the chemical industry is that only a single reactor and process is necessary for the different molecules and only a fraction of the infrastructure investment is required compared to the chemical industry.

Classifications

There are different classifications of Industrial Biotechnology. One of the most reviewed is based on feedstocks:

• 1G: the First generation is food crops for the production of high-value molecules
• 2G: the Second generation are non-food cellulosic feedstock for low-value molecules like biofuels
• 3G : the Third generation of processes based on GHG, CO2, algae and Industrial waste

Another classification is based on applications:

• Chemical Industry: low-volume, high-value molecules
• Fuel Industry: high-volume, low-value biofuels
• Acellular Agriculture : animal free meat, protein revolution
• Special applications : replacement of high-quality products (spider silk, leather)

Demarcation to Synthetic Biology

Industrial Biotechnology is an area of synthetic biology. As mentioned above under safety, the products manufactured with methods of industrial biotechnology do not contain genetically modified parts or molecules. Other areas in synthetic biology are in the business of genetically modified animals or plants in order to introduce desired properties or to exclude negative effects. These areas cannot be associated with Industrial Biotechnology.

Demarcation to Biotech and replacement of Biotech processes

Biotech or red Biotechnologie is applied to medical processes (Biomedicine, Biopharmaceutics, Diagnostics) and to date, both areas overlap only to a small extent. Biotech is predominantly working with mammalian cells and Industrial Biotechnology predominantly working with yeast. Biotech is a multibillion-dollar market and is closely followed by many institutions. Biotech companies are not tracked in the industrial Biotechnology Index as long as they do not use yeast as described below.

Companies in Industrial Biotechnology will use yeast and other microorganisms as alternatives to mammalian cell lines for the production of therapeutic recombinant proteins. Monoclonal antibodies are traditionally produced by means of cultivated mammalian cells in large bioreactors. The Cho Cell line abbreviated by English Chinese hamster Ovary is one of the most commonly used cell lines in the biotechnological production of active ingredients. However, such cultures develop slowly, require complex media, are sensitive to viral infections and often result in only a low yield. The safety requirements when working with such bioreactors are very high and incur a correspondingly high cost. The separation of the desired antibody is very laborious, as undesired often 10 different forms are produced simultaneously. Yeast cell factories combine the advantages of being single cells, such as fast growth and easy genetic manipulation, as well as eukaryotic features including a secretory pathway leading to correct protein processing and post-translational modifications. In this respect, especially the engineering of yeast glycosylation to produce glycoproteins of human-like glycan structures is of great interest. Terpenoids show a wide range of biological activities and are already used as medicines (artemisinin, taxol). Terpenoids are often difficult to produce via chemical processes or in red Biotech. The industrial biotechnology with the genetically modified metabolic pathways can show new ways to produce known or derived terpenoids. In the future, more and more pharmaceutical products manufactured with processes in Industrial Biotechnology and based on terpenoids will be introduced, which will play a more important role in the pharmaceutical market.

Cellfree processes

Another interesting development is the production of products in a cell-free environment. The fermentation process with living organisms is thereby replaced by a development process in which only the necessary constituents from the cells are used. However, the development of such production processes is still in the research phase, and it will be shown whether the fermentation processes are displaced.

Future impact

Industrial Biotechnology will have great impact to really change our lives and make the planet healthier. Industrial Biotechnology has just scratched the surface but within 2 to 3 years the introduction of new molecules and applications will rush and Industrial Biotechnology will begin to show its influence in many areas of our life. Industrial Biotechnology will soon become a major participant in the modern global industry. The best is yet to come, as microbes move into the chemicals, environmental and health sectors. As stated many years ago by Louis Pasteur, “The microbe will have the last word.”