February 17, 2023
Fermentation has been with mankind at least since the first settlements in the Middle East about 12,000 years ago. Of course, nothing was known about the organisms or mechanisms that cause food to ferment. The results of food fermentation for preservation were considered so valuable that they were attributed to the gods.
Today, scientists have gained so much knowledge about microorganisms and the fermentation process that pharmaceutical manufacturers are using it for the production of vaccines or bioconjugates like ADCs (antibody-drug conjugates) and the development of advanced therapies.
In this article we will take a closer look at microbial fermentation and what milestones have led to today’s fermentation technology.
First, the question “what is microbial fermentation?” should be answered. In biochemistry, fermentation is defined as the extraction of energy from substrates by enzymes without the use of oxygen. This can occur in a container with ripening kimchi or in the muscles of high performance athletes when the supply of oxygenated blood is limited, but it can also occur in cells. Microbial fermentation means that an ecosystem of microbes brings about the process of fermentation.
There are 3 types of fermentation, like lactic acid fermentation, acetic acid fermentation of alcoholic fermentation. Learn more about the types of fermentation in the article: microbial fermentation simply explained.
Now we are all on the same page and ready to take a quick look at the history of fermentation and shift our focus from food production to biopharmaceutical manufacturing by biotechnology.
Image: Louis Pasteur developed the process of pasteurization (1856)
The very earliest examples of man-made fermented foods date back about twelve millennia. The climatic conditions in northern Africa are ideal for fermenting milk of camels, sheep, goats and cattle. Under these conditions and the natural microbial cultures present, fermentation occurred easily. The results resembled yogurt and has a relatively long shelf life. Further processing resulted in cheese-like foods that are very high in calories and nutrients and perfect for feeding people in the harsh Neolithic living conditions.
Until recently, archaeological research in Iran assumed that the first alcoholic beverages date back to about 5,500 BC. Scientists discovered that the Chinese already brewed 1,500 years earlier. Careful chemical analysis of Neolithic pottery revealed that fruits, rice and honey were fermented and used to create alcoholic brews: the same ingredients used in today’s wine, sake and mead.
2,500 years ago, the Chinese discovered the medical value of preparations made from fermented soybeans: the microbes in the moldy soybean curd produced antibacterial secondary metabolites that helped treat infected wounds, boils and carbuncles. Although they had no scientific understanding of what was going on, phenomenologically they were over two millennia ahead of Fleming, the discoverer of penicillin.
At this time many cultures began to use fermentation to preserve, refine and create foods. Sauerkraut in Europe, kimchi in Eastern Asia, kefir and fermented dairy products in North Africa, all great examples of conserving essential foods while keeping their nutritional value high. Additionally, the use of microbes in sourdough enables farmers to unlock the sustenance of rye.
These peoples applied the knowledge of many generations before them to secure their supplies.
Two centuries after its discovery by van Leeuwenhoek, Louis Pasteur, the famous French scientist, deepened and widened our understanding of fermentation and the action of microbes. He concluded that fermentation and spoilage require live microorganisms. His investigations with elevated temperatures led to the development of the preservation technique that carries his name: pasteurization.
Designer probiotics have been commercially available since the 1970s. They consist of various microbial strains designed to promote gastrointestinal health. The general concept of probiotics was first described in ancient China. Russian biologist Elie Metchnikoff discovered the health benefits of Lactobacillus acidophilus about 60 years earlier.
The Russian bacteriologist Elie Metchnikoff researched bacterial strains and discovered a particularly long-lived Lactobacillus strain in milk, which he called the Bulgarian bacillus. It was later renamed Lactobacillus acidophilus, which has become very well known for its high activity in the human digestive system.
Today, microbes are in charge of the synthesis of much of the world’s productivity of complex pharmaceutical molecules. Their biochemical machinery of enzymes is capable of performing the most sophisticated chemical tasks very efficiently, much better than laboratory chemists could. Therefore, precision fermentation using specialized strands of bacteria, fungi or yeast, probably optimized with recombinant technology, is widely used to produce raw materials for further (bio)chemical refinement.
This is done in large bioreactors, where the microbes grow in culture media that supplies them with nutrients (amino acids and energy sources), minerals and appropriate pH, oxygen and carbon dioxide levels. In turn, the microbes produce the desired compounds, e. g. proteins, peptides, lipids, complex carbohydrates, secondary metabolites like penicillins and macrolides etc. When the concentration of desired products is highest, the fermentation broth is subjected to downstream processing to concentrate and isolate the product.
These processes are used to manufacture vaccine components, antiinfectives, anticancer therapies and many more.
Our understanding of fermentation has come a long way from a devine gift to its use in modern microbiology and complete control by recombinant molecular biology. The application of microbial fermentation in the production of pharmaceutical products will lead to highly energy and cost efficient processes and their impact is expected to grow in the future.
Single Use Support developed beneficial end-to-end solutions for bulk filling and cold chain handling. The latest developments in fermentation are bringing more and more biopharmaceutical applications. This means that Single Use Support is also addressing manufacturing challenges and is finding optimized solutions for efficient, fully automated filling and freezing of liquids for safe handling and transport in precision fermentation. Taking this new advancements into account the process solution provider is striving to transfer its expertise in single-use technology to the growing field of microbial fermentation.
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