Industrial Fermentation

Summary

Industrial fermentation is an interdisciplinary science that applies principles associated with biology and engineering. The biological aspect focuses on microbiology and biochemistry. The engineering aspect applies fluid dynamics and materials engineering. Industrial fermentation is associated primarily with the commercial exploitation of microorganisms on a large scale. The microbes used may be natural species, mutants, or microorganisms that have been genetically engineered. Many products of considerable economic value are derived from industrial fermentation processes. Many common products are produced via industrial fermentation—antibiotics, cheese, pickles, wine, beer, biofuels, vitamins, amino acids, solvents, and biological insecticides and pesticides.

Definition and Basic Principles

Industrial fermentation uses living organisms (mainly microorganisms), typically on a large scale, to produce commercial products or perform necessary chemical transformations. The goal of industrial fermentation is to improve biochemical or physiological processes that microbes are capable of performing while yielding the highest quality and quantity of a particular product. The development of fermentation processes requires knowledge from disciplines such as microbiology, biochemistry, genetics, chemistry, chemical and bioprocess engineering, mathematics, and computer science. The major microorganisms used in industrial fermentation are fungi (such as yeast) and bacteria. Fermentation is performed in large fermenters or other bioreactors, often of several thousand liters in volume. Industrial fermentation is a part of many industries, including microbiology, food, pharmaceutical, biotechnology, and chemical.

Background and History

Traditional fermentations, such as those for making bread, cheese, yogurt, vinegar, beer, and wine, had been used by people for thousands of years before their microbial nature was understood. Brewing beer was one of the first applications of fermentation in ancient Egypt as long as 10,000 years ago. The exact origins of dairy products are unknown—it may have been as early as 8000 BCE. It was probably nomadic Turkish peoples in Central Asia who invented cheese and yogurt making. Traditionally, dairy fermentation was a means of milk preservation. The scientific understanding of fermentation began only in the nineteenth century after French scientist Louis Pasteur published the results of his studies on the microbial nature of wine-making.

The first industrial fermentation bioprocesses based on knowledge of microbes appeared in the early twentieth century. Russian biochemist Chaim Weizmann is considered to be the father of industrial fermentation. Weizmann used the bacterium Clostridium acetobutylicum in 1916 to produce acetone from starch, called the ABE (Acetone Butanol Ethanol) fermentation process. This was used to make explosives during World War I. The bacteria is sometimes called the Weizmann organism after its discoverer.

Significant growth in this field began in the middle of the twentieth century when the fermentation process for the large-scale production of antibiotic penicillin was developed. The goal of the industrial-scale output of penicillin during World War II led to the development of fermenters by engineers who were working together with biologists from the pharmaceutical company Pfizer. The fungus Penicillium grows and produces an antibiotic much more effectively under controlled conditions inside the fermenter. Continuous progress in industrial fermentation technology in the twentieth century has followed the development of genetic engineering. Genetic engineering allows gene transfer between species and creates possibilities to generate new products from genetically modified microorganisms grown in fermenters.

The twenty-first century has been characterized by the introduction of biofuels, which are made by industrial fermentation processes. Once again, past and future developments in fermentation technology require contributions from a wide range of disciplines, including microbiology, genetics, biochemistry, chemistry, engineering, mathematics, and computer science.

How It Works

Industrial fermentation is based on microbial metabolism. Microbes produce different kinds of substances that they use to grow and maintain their cells. These substances can be useful for humans. Industrial fermentation technology aims to enhance the microbial production of useful substances. Most industrial fermentation occurs in liquid, but for products such as miso, coffee, and cocoa, a moist fermentation process occurs.

Process of Fermentation. In biology, fermentation is a process of harvesting energy of organic molecules in oxygen-free conditions. Sugars are a prime example of what can be fermented, although many other organic molecules can be used. Different fermentations are known and categorized by the substrate metabolized or the product type. In industry, any large microbiological process is called fermentation. Thus, the term fermentation has a different meaning than in biology. Most industrial fermentations require oxygen.

Industrial Fermentation Organisms. Organisms like bacteria, fungi, and plant and animal cells are used in industrial fermentation processes. An industrial fermentation organism must produce the product of interest in high yield, grow rapidly on inexpensive culture media available in bulk quantities, be open to genetic manipulation, and be nonpathogenic (does not cause any diseases).

Fermentation Media. To make a desired product by fermentation, microorganisms need nutrients (substrates). Nutrients for microbial growth are known as media. Most fermentation requires liquid media or broth. General media components include carbon, nitrogen, oxygen, and hydrogen in the form of organic or inorganic compounds. Other minor or trace elements must also be supplied, for example, iron, phosphorus, or sulfur.

Fermentation Systems. Industrial fermentation takes place in fermenters, which are also called bioreactors. Fermenters are closed vessels (to avoid microbial contamination) that reach vast volumes, as many as several hundred thousand liters. Designed by engineers, the primary purpose of a fermenter is to provide controllable conditions for the growth of microbial cells or other cells. Parameters such as pH, temperature, nutrients, fluid flow, and other variables are controlled. There are two kinds of fermenters—anaerobic processes (oxygen-free) and aerobic processes. Aerobic fermentation is the most common in industry. Anaerobic fermenters can be as simple as stainless-steel tanks or barrels. Aerobic fermenters are more complicated. The most critical part of these systems is aeration. In a large-scale fermenter, the transfer of oxygen is essential. Oxygen transfer and dispersion are provided by stirring with impellers or oxygen (air) sparging.

Fermentation Control and Monitoring. Industrial fermentation control is very important to ensure that organisms behave properly. In most cases, computers are used to control and monitor the fermentation process. Computers control temperature, pH, cell density, oxygen concentration, level of nutrients, and product concentration.

Applications and Products

There is a wide range of industrial fermentation products and applications.

Food, Beverages, Food Additives, and Supplements. Industrial fermentation plays a major role in the production of food. Food products traditionally made by fermentation include dairy products (cheeses, sour cream, yogurt, and kefir); food additives and supplements (flavors, proteins, vitamins, and carotenoids); alcoholic beverages (beer, wines, and distilled spirits); plant products (bread, coffee, soy sauce, tofu, sauerkraut); and fermented meat and fish (pepperoni and salami).

Industrial Fermentation. The primary and largest industry revolves around food products. Milk from cows, sheep, goats, and horses has traditionally been used to produce fermented dairy products. These products include cheese, sour cream, kefir, and yogurt. In the twenty-first century, so-called probiotics have appeared and been marketed as health-food drinks. Dairy products are produced via fermentation using lactic bacteria such as Lactobacillus acidophilus and Bifidobacterium. Fungi are also involved in making some cheeses. Fermentation produces lactic acid, and other flavors and aroma compounds that make dairy products taste good.

Many industrial fermentation products are added to food as flavors, vitamins, colors, preservatives, and antioxidants. These products are more desirable than food additives produced chemically. Many of the vitamins are made by microbial fermentations, including thiamine (vitamin B₁), riboflavin (vitamin B₂), cobalamin (vitamin B₁₂), and vitamin C (ascorbic acid). Vitamin C is not only a vitamin but also an important antioxidant that helps prevent heart diseases. Carotenoids are another effective antioxidant. They are also used as a natural food color for butter and ice cream. Carotenoids are red, orange, and yellow pigments produced by bacteria, algae, and plants.

Food preservatives are yet another product of industrial fermentation. Organic acids, particularly lactic and citric acids, are extensively used as food preservatives. Some preservatives, like citric acid, are used as flavoring agents. A mixture of two bacterial species (Lactobacillus and Streptococcus) is usually used for industrial lactic acid production. The mold Aspergillus niger is used for citric acid manufacturing. Another common preservative is the protein nisin. Nisin is produced via fermentation by the bacterium Lactococcus lactis. It is employed in the dairy industry, especially for producing processed cheese.

Antibiotics and Other Health Care Products. Antibiotics are chemicals produced by fungi and bacteria that kill or inhibit the growth of other microbes. They are the second most significant product of industrial fermentation. Most antibiotics are generated by molds or bacteria called actinomycetes. Over 4,000 antibiotics have been isolated from microorganisms, but only about 50 are produced regularly. Among them, beta-lactams, such as penicillins and tetracyclines, are the most common. Penicillin is produced by the mold Penicillium chrysogenum via corn fermentation in bioreactors of up to 200,000 liters (52,835 gallons).

The other major healthcare products produced with the help of industrial fermentation are bacterial vaccines, therapeutic proteins, steroids, and gene therapy vectors. There are two categories of bacterial vaccines—living and inactivated vaccines. Living vaccines consist of weakened, also known as attenuated, bacteria. Examples of live vaccines include those for diseases such as anthrax, which is caused by Bacillus anthracis, and typhoid fever, which is caused by Salmonella typhi. Inactivated vaccines are composed of bacterial cells or parts that have been inactivated by heat or formaldehyde. Examples of these vaccines are those for meningitis, whooping cough, and cholera. Vaccine production takes place in fermenters that are no bigger than 1,000 liters in volume. It requires highly controlled operations to avoid the release of bacteria into the environment. All exhaust gases pass through sterilization processes.

Therapeutic proteins include growth hormone, insulin, wound-healing factors, and interferon. Previously, such compounds were made from animal tissues and were very expensive to manufacture. Genetic engineering now allows their production by fermentation from bacteria. Human growth hormone is synthesized in the human brain and controls growth. Too little growth hormone can cause some cases of dwarfism. The American company Genentech started production of human growth hormone from genetically modified Escherichia coli by fermentation in 1985. Insulin is an animal and human hormone that is involved in the regulation of blood sugar. The body’s inability to make sufficient insulin causes diabetes. Insulin extracted from pigs has been used to treat diabetes but has been replaced by insulin produced by industrial fermentation from genetically modified bacteria.

Chemicals. Numerous chemicals, such as amino acids, polymers, organic acids (citric, acetic, and lactic), and bioinsecticides are produced by industrial fermentation. Amino acids are used as food and animal feed, as well as in the pharmaceutical, cosmetic, and chemical industries. Bacteria such as Micrococcus luteus and Corynebacterium glutamicum are used for industrial fermentation to produce chemicals. Bacterial toxins are effective against different insects. Since the 1960s, preparations of the bacteria Bacillus thuringiensis have been produced by fermentation as a biological insecticide.

Enzymes. Enzymes are used in many industries as catalysts. Microorganisms are the favored source of industrial enzymes. Seventy percent of these enzymes are made from Bacillus bacteria via fermentation. Most commercial microbial enzymes are hydrolases, which break down different organic molecules such as proteins and lipids. The enzyme glucose isomerase is important in the production of fructose syrups from corn and is widely used in the food industry.

Biomass Production. During biomass production by fermentation, the cells produced are the products. Biomass is used for four purposesas a source of protein for human food or animal feed, in industry as fermentation starter cultures, in agriculture as a pesticide or fertilizer, and as a fuel source.

One major product of this industrial fermentation application is baker’s yeast biomass. Baker’s yeast is required for making bread, bakery products, beer, wine, ethanol, microbial media, vitamins, animal feed, and biochemicals for research. Yeast is produced in large aerated fermenters of up to 200,000 liters. Molasses is used as a nutrient source for the cells. Yeast is recovered from fermentation liquid by centrifugation and then dried. It can then be sold as compressed yeast cakes or dry yeast.

Many bacteria have been considered potential sources of protein to fulfill the food needs in some countries. Among the few species cultivated for food and feed, cyanobacteria are the most popular. The protein level of Cyanobacterium spirulina can be as high as that found in meat, nuts, and soybeans, at 50 to 70 percent. This cyanobacterium has been used as human food for millennia in Asia, parts of Africa, and Mexico.

Apart from yeast and bacteria, people also use the biomass of algae. Algae are a source of animal feed, plant fertilizer, chemicals, and biodiesel. Because light is necessary to grow algae, the biomass is produced in open ponds or in transparent tubular glass or plastic bioreactors, called photobioreactors.

Biofuels. Industrial fermentation is used to produce biofuels, mainly ethanol and biogas. These two biofuels are produced by the action of microorganisms in bioreactors. Fermentation can also be used to generate biodiesel, butanol, and biohydrogen. Many consider biofuels to be a future substitute for fossil fuels. Pollution from fossil fuels affects public health and causes global climate change due to carbon dioxide (CO₂) release. Using biofuels as an energy source generates less pollutants and little or no CO₂.

Production of ethanol is a process based on fungal or bacterial fermentation of a variety of materials. In the United States, most of the ethanol is produced by yeast (fungal) fermentation of sugar from cornstarch, though sugarcane is another and often more efficient source. Sugar is extracted using enzymes, and then yeast cells convert the sugar into ethanol and CO₂. Ethanol is separated from the fermentation broth by distillation.

Biogas is produced during the anaerobic (non-oxygen) fermentation of organic matter by communities of microorganisms (bacteria and Archaea). There are different types of biogas. One type contains a mixture of methane (50 to 75 percent) and CO₂. Another type is composed primarily of nitrogen, hydrogen, and carbon monoxide (CO) with trace amounts of methane. Methane is generated by microorganisms called Archaea and is an integral part of their metabolism. For practical use, biogas is generated from wastewater, animal waste, and “gas wells” in landfills.

Careers and Course Work

There are several career options for people who are interested in being trained in industrial fermentation. Food, biotechnology, microbiology, pharmaceutical, chemical, and biofuel companies are the biggest employers in the area. Students who are interested in conducting research in industrial fermentation can find jobs in university, government, and industry laboratories.

When choosing a career in industrial fermentation, one should be prepared for an interdisciplinary science. The applied science, called zymurgy or sometimes zymology, studies fermentation at the biochemical level. If these courses are unavailable, students should obtain microbiology, molecular biology, bioengineering, plant biology, organic chemistry, biochemistry, agriculture, bioprocess engineering, and chemical engineering skills.

Most industrial fermentation professionals have a bachelor’s degree in biology, microbiology, or biotechnology. Individuals with managerial responsibilities often have a master’s or doctorate in biology, microbiology, fermentation, molecular biology, biochemistry, biotechnology, bioprocess or chemical engineering, or genetics. Some universities offer degrees in fermentation or related topics. The University of California, Davis, provides a degree in food science and technology, and Oregon State University offers a bachelor’s degree in food technology and fermentation science. Central Michigan University offers a certificate in fermentation science for a shorter study path. Several universities, including Auburn, Colorado State, and Portland State, offer brewing science certificates, courses, or degrees.

A career in industrial fermentation presents various work options, such as research, process development, production, technical services, or quality control. Some industrial fermentation specialists may be considered genetic engineers (using DNA techniques to modify living organisms). Others are classified as bioprocess or chemical engineers (optimizing bioreactors and biochemical pathways for a desired product).

Social Context and Future Prospects

Industrial fermentation plays a major role in providing food, chemicals, and fuels. End users are consumers, farmers, medical doctors, and industrialists. Industrial fermentation has changed the course of history. People have made food by fermentation for centuries, but the rise of modern industry took production to new levels. In the twentieth century, the development of antibiotics and their production by industrial fermentation had a significant impact on the practice of medicine.

The growth of the industrial fermentation field is continuing rapidly. In the early twenty-first century, industrial fermentation underwent an unprecedented growth and expansion due to biofuel introduction. Medical research into intestinal microbiomes and their impact on health has also boosted industrial fermentation. Food products such as kombucha, a fermented tea, have commanded an increasing share of the market driven by health-conscious consumers. The role of industrial fermentation in society is likely to only expand in the future because of increasing requirements for resources and a deeper understanding of the benefits of fermented foods.

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