CHAPTER 30 Industrial Microbiology
Industrial Microorganisms and Product Formation Industrial Microorganisms and Their Products
The actual reactions carried out by microorganisms in industrial microbiology are called biocatalysis (Figure 30.1). Industrial microbiology uses microorganisms, typically grown on a large scale, to produce valuable commercial products or to carry out important chemical transformations.
An industrial microorganism must produce the product of interest in high yield; grow rapidly on inexpensive culture media available in bulk quantities; be amenable to genetic manipulation; and, if possible, be nonpathogenic. There are many industrial products, including both cells and substances made by cells. • Commodity chemicals are inexpensive chemicals produced in bulk, including ethanol, citric acid, and many others.
Primary and Secondary Metabolites Primary metabolites are produced during active cell growth, and secondary metabolites are produced near the onset of stationary phase (Figure 30.2).
Figure 30.3 shows the interrelationship of the main primary metabolic pathway for aromatic amino acid synthesis • and the secondary metabolic • pathways for a variety of • antibiotics.
Characteristics of Large-Scale Fermentations Large-scale industrial fermentation presents several engineering problems. Aerobic processes require mechanisms for stirring and aeration.
The microbial process must be continuously monitored to ensure satisfactory yields of the desired product.
Industrial fermentors can be divided into two major classes, those for anaerobic processes and those for aerobic processes (Figure 30.4).
Fermentation Scale-Up Fermentation scale-up is the process of gradually converting a useful industrial fermentation from laboratory scale to production scale. Aeration is a particularly critical aspect to monitor during scale-up studies.
Major Industrial Products for the Health Industry Antibiotics: Isolation and Characterization
The industrial production of antibiotics begins with screening for antibiotic producers (Figure 30.7).
Once new producers are identified, purification (Figure 30.8) and chemical analyses of the antimicrobial agent are performed.
If the new antibiotic is biologically active in vivo, the industrial microbiologist may genetically modify the producing strain to increase yields to levels acceptable for commercial development.
Major antibiotics of clinical significance include the -lactam antibiotics penicillin (Figure 30.9) and cephalosporin and the tetracyclines (Figure 30.11).
Cephalosporins are valued clinically not only because of their low toxicity but also because they are broad-spectrum antibiotics, useful against a wide variety of bacterial pathogens.
Figure 30.10 shows the kinetics of the penicillin fermentation with Penicillium chrysogenum.
If the penicillin fermentation is carried out without addition of side-chain precursors, the natural penicillins are produced. The fermentation can be more directed by adding to the broth a side-chain precursor so that only one desired penicillin is produced.
The product formed under these conditions is referred to as a biosynthetic penicillin. To produce the most useful penicillins, those with activity against gram-negative Bacteria, a combined fermentation and chemical approach is used that leads to the production of semisynthetic penicillins. • All of these antibiotics are typical secondary metabolites, and their industrial production is well worked out despite the fact that the biochemistry and genetics of their biosynthesis are only partially understood.
Vitamins and Amino Acids Vitamins produced microbially include vitamin B12 and riboflavin (Figure 30.12).
The most important amino acids produced commercially are glutamic acid, aspartic acid, phenylalanine, and lysine (Figure 30.13).
Aspartic acid and phenylalanine are the ingredients of the artificial sweetener aspartame, a non-nutritive sweetener of diet soft drinks and other foods sold as low-calorie or sugar-free products.
High yields of amino acids are obtained by modifying regulatory signals that control synthesis of the particular amino acid such that overproduction occurs.
Steroids and the Biotransformation Process Microbial biotransformation employs microorganisms to biocatalyze a specific step or steps in an otherwise strictly chemical synthesis (Figure 30.14).
Enzymes as Industrial Products Microorganisms are ideal for the large-scale production of enzymes. Many enzymes are used in the laundry industry to remove stains from clothing, and thermostable and alkalistable enzymes have many advantages in these markets.
These extracellular enzymes, called exoenzymes, can digest insoluble polymers such as cellulose, protein, and starch. The products of digestion are then transported into the cell where they are used as nutrients for growth. Certain enzymes are produced in large amounts by some organisms, and instead of being held within the cell, they are excreted into the medium.
The term extremozyme has been coined to describe enzymes that function at some environmental extreme, such as high temperatures or low pH (Figure 30.15). Enzymes from extremophiles are desirable for biocatalyses under extreme conditions.
For some biocatalytic processes, it is desirable to fix soluble enzymes onto a solid surface. These are called immobilized enzymes (Figure 30.16).