Certain properties make microorganisms well suited for industrial processes. Microorganisms not only possess a broad variety of enzymes to make an array of chemical conversions possible, but they also have a relatively high metabolic activity that permits conversions to take place rapidly.
In addition, they have a large surface area for quick absorption of nutrients, and release of end-products. Moreover, they usually multiply at a high rate, as evidenced by the 20-minute generation time for Escherichia coli under ideal conditions.
In the industrial process, microorganisms act like chemical factories. To be effective, they should liberate a large amount of a single product that can be efficiently isolated and purified. The microorganisms should be easy to maintain and cultivate, and should have genetic stability with infrequent mutations.
Their value is enhanced if they can grow on an inexpensive, readily available medium that is a by-product of other industrial processes. For example, a large amount of whey is produced in cheese manufacturing, and microorganisms that convert whey components to lactic acid add to the overall profit of the cheese industry.
Production of Organic Compounds:
Microorganisms are used in industry to produce a variety of organic compounds including acids, growth stimulants, and enzymes. In some cases the production results from an apparent accident in nature where an organism manufactures many thousands of times the amount necessary for its own metabolism.
One of the first organic acids to be made in bulk by microorganisms was citric acid. Manufacturers use this organic compound in soft drinks, candies, inks, engraving materials, and in a variety of pharmaceuticals such as anticoagulants and effervescent tablets (Alka-Seltzer). The organism most widely used in citric acid production is the mold Aspergillus niger.
Microbiologists inoculate the mold to a medium of corn meal, molasses, salts, and inorganic nitrogen in huge shallow pans or fermentation tanks. The absence of a Krebs cycle enzyme in the mold prevents the metabolism of citric acid into the next component of the cycle, and the citric acid accumulates in the medium.
Another important microbial product is lactic acid, a compound employed to preserve foods, finish fabrics, prepare hides for leather, and dissolve lacquers. Lactic acid is commonly produced by bacterial activity on the whey portion of milk. Lactobacillus bulgaricus is widely used in the fermentation because it produces only lactic acid from lactose.
Gluconic acid, another valuable organic acid, is useful in medicine as a carrier for calcium, because gluconic acid is easily metabolized in the body leaving a store of calcium for distribution. This acid is produced from carbohydrates by A. niger and species of the bacterium Gluconobacter cultivated in fermentation tanks. Calcium gluconate is also added to the feed of laying hens to provide calcium that strengthens the eggshells.
When the amount of amino acid produced by a microorganism exceeds the need, the remainder is excreted into the environment. Such is the case with glutamic acid produced by certain species of Micrococcus, Arthrobacter, and Brevibacterium. Glutamic acid is a valuable food supplement for humans and animals, and its sodium salt, monosodium glutamate, is utilized in food preparations.
In the production of lysine, another amino acid, two organisms are involved. E. coli is first cultivated in a medium of glycerol, corn steep liquor, and other ingredients, and the compound diaminopimelic acid (DAP) accumulates. Several days later, Enterobacter aerogenes is added to the mixture. This organism produces an enzyme that removes the carboxyl group from DAP to produce the lysine used in breads, breakfast cereals, and other foods.
Two important vitamins, riboflavin (vitamin B2) and cyanocobalamin (vitamin B12), are also products of microbial growth. Riboflavin is a product of Ashbya gossypii, a mold that produces 20,000 times the amount it needs for its metabolism. Cyanocobalamin is produced by selected species of Pseudomonas, Propionibacterium, and Streptomyces grown in a cobalt-supplemented medium. The vitamin prevents pernicious anemia in humans and is used in bread, flour, cereal products, and animal feeds.
Enzymes and Other Products:
The production of microbial enzymes for commercial exploitation has been an important industry since the emergence of industrial microbiology. Currently, over two dozen types of microbial enzymes are in use, and several others are in the research or developmental stage.
The important microbial enzymes include amylase, pectinase, and several proteases. Amylase is produced by the mold Aspergillus oryzae. It is used as a spot remover in laundry presoaks, as an adhesive, and in baking, where it digests starch to glucose. Pectinase, a product of a Clostridium species, is employed to ret flax for linen.
In this process, manufacturers mix the flax plant with pectinase to decompose the pectin “cement” that holds cellulose fibers together. The cellulose fibers are then spun into linen. Pectinase is also used to clarify fruit juices.
Proteases are a group of protein-digesting enzymes produced by Bacillus subtilis, Aspergillus oryzae, and other microorganisms. Certain proteases are used for bating hides in leather manufacturing, a process in which organic tissue is removed from the skin to yield a finer texture and grain. Other proteases find value as liquid glues, laundry presoaks, meat tenderizers, drain openers, and spot removers.
One of the most appreciated but lesser known uses of a microbial enzyme is in making soft-centered chocolates. Invertase, an enzyme from yeast, is mixed with flavoring agents and solid sucrose, and then covered with chocolate. The enzyme converts some of the sucrose to liquid glucose and fructose, forming the soft center of the chocolate.
In medical microbiology, doctors use another microbial enzyme, streptokinase, to break down blood clots formed during a heart attack. Still another enzyme, hyaluronidase, is used to facilitate the absorption of fluids injected under the skin.
Gibberellins are a series of plant hormones that promote growth by stimulating cell elongation in the stem. Botanists use the hormones to hasten seed germination and flowering, and agriculturalists find them valuable for setting blooms in the plant. This increases the yield of fruit and in the case of grapes, enhances their size. Gibberellins are produced during the metabolism of the fungus Gibberella fujikuroi and may be extracted from these organisms for commercial use.
In addition to the major products that we have surveyed, microorganisms provide a number of specialized materials. Typical of the miscellaneous microbial products is alginate, a sticky substance used as a thickener in ice cream, soups, and other foods. Another product of microbial origin is perfume. Musk oil, for example, is prepared from ustilagic acid, a product of the mold Ustilago zeae, which, ironically, causes smut disease.
Production by purely chemical means is prohibitively expensive. Moreover, there are numerous pharmaceutical products derived from the ergot poisons of the mold Claviceps purpurea. These derivatives are prescribed to induce labor, treat menstrual disorders, and control migraine headaches.
Other Microbial Products:
In addition to the products we have discussed, microorganisms are the sources of antibiotics and a number of valuable insecticides. Moreover, they are the biological factories for the genetic engineering technology that has revolutionized industrial microbiology. In the final section of this text, we shall study the methods for antibiotic and insecticide production and discuss some details of the genetic engineering process.
Antibiotics:
Penicillin was the first antibiotic to be produced on an industrial scale. In 1941, Robert H. Coghill of the Fermentation Division of the XJSDA made the suggestion that the deep-tank method used to produce vitamins might be applied to penicillin.
In the ensuing months he offered several modifications to stimulate the growth of Penicillium notatum and increase the penicillin yield. For example, corn steep liquor in the culture medium increased the output 20 times, and substitution of lactose for glucose made penicillin production still more efficient.
Moreover, the search for a higher-yielding producer of the drug led researchers to Penicillium chrysogenum, a mold isolated from a rotten canteloupe from a Peoria, Illinois, supermarket. Treatment with ultraviolet light resulted in a mutant with still higher penicillin yields. By 1943, the United States was producing enough penicillin for the allied forces, and by 1945 sufficient amounts were available for the civilian population.
To the present time, over 5000 antibiotic substances have been described and approximately 100 such drugs are available to the medical practitioner. Although most antibiotics are produced by species of Streptomyces, a significant number are products of Penicillium or Bacillus species. The worldwide production of antibiotics exceeded 25,000 tons in 1990, and two-thirds were penicillins.
Antibiotic production is carried on in huge, aerated tanks of stainless steel similar to those used in brewing. A typical tank may hold 30,000 gallons of medium. Older methods employed enormous mats of fungus or actinomycetes on the surface of the tank. Newer technology, however, employs small fragments of submerged hyphae or cells, rotated and agitated in the medium with a constant stream of oxygen.
After several weeks of growth, the microorganisms are removed, and the antibiotic is extracted from the medium for further conversion to the desired product. The remaining brown mash of microorganisms may be dried and sold as an animal feed additive. Another alternative is to process it for use as human food.