Fermentation process products

Biotechnological processes may be divided into fermentation processes and biotransformations. In a fermentation process, products are formed from components in the fermentation broth, as primary or secondary metabolites, by microorganisms or higher cells. Product examples are amino acids, vitamins, or antibiotics such as penicillin or cephalosporin. In these cases, co-solvents are sometimes used for in situ product extraction. 

The alteration of fermentation conditions, such as pH, drastically affects product concentrations. Research with C. ljungdahlii has shown that at high pH values (5.5-6), acetate was the dominant product, while at a lower pH (4-4.5), there was a drastic shift towards the production of ethanol. " Inhibition by end products or intermediates is the principal factor that limits metabolic rates and final product concentrations in many fermentation processes. Product inhibition can greatly affect the economics of commercialization. With regards to ethanol inhibition, growth of B. methylotrophicum was inhibited at alcohol concentrations of 5g/L. " However, a recently isolated clostridial strain was shown to tolerate ethanol concentrations up to 78g/L. Efforts have been made to eliminate the drawbacks of inhibition by improvement of bacterial strains to tolerate higher product concentrations and/or by use of novel separation coupled fermentation processes such as pervaporation, extraction, and membrane separation. 

Manufactured by the liquid-phase oxidation of ethanal at 60 C by oxygen or air under pressure in the presence of manganese(ii) ethanoate, the latter preventing the formation of perelhanoic acid. Another important route is the liquid-phase oxidation of butane by air at 50 atm. and 150-250 C in the presence of a metal ethanoate. Some ethanoic acid is produced by the catalytic oxidation of ethanol. Fermentation processes are used only for the production of vinegar. 

With the proper ratio of nutrients and oxygen feed, a water-soluble polymer is produced and accompanied by growth in the microorganism population. Both contribute to the viscosity of the medium and this limits the production process. Fermentation processes require more strenuous mixing and control conditions. 

Although a tremendous number of fermentation processes have been researched and developed to various extents, only a couple of hundred ate used commercially. Fermentation industries have continued to expand in terms of the number of new products on the market, the total volume (capacity), and the total sales value of the products. The early 1990s U.S. market for fermentation products was estimated to be in the 9-10 x 10 range. The total world market is probably three times that figure, and antibiotics continue to comprise a primary share of the industry. Other principal product categories are enzymes, several organic acids, baker s yeast, ethanol (qv), vitamins (qv), and steroid hormones (qv). 

Fig. 2. Schematic representation of a fermentation process for an extracellular product.

Generally, for most fermentation processes to yield a good quality product at a competitive price, at least six key criteria must be met. (/) Fermentation is a capital intensive business and investment must be minimised. (2) The raw materials should be as cheap as possible. (J) Only the highest yielding strains should be used. (4) Recovery and purification should be as rapid and as simple as possible. (5) Automation should be employed to minimise labor usage. (6) The process must be designed to minimise waste production and efftciendy use all utilities (26,27). 

Lactic acid-producing bacteria associated with fermented dairy products have been found to produce antibiotic-like compounds caUed bacteriocins. Concentrations of these natural antibiotics can be added to refrigerated foods in the form of an extract of the fermentation process to help prevent microbial spoilage. Other natural antibiotics are produced by Penicillium wqueforti the mold associated with Roquefort and blue cheese, and by Propionibacterium sp., which produce propionic acid and are associated with Swiss-type cheeses (3). 

Biological—Biochemical Processes. Fermentation is a biological process in which a water slurry or solution of raw material interacts with microorganisms and is enzymatically converted to other products. Biomass can be subjected to fermentation conditions to form a variety of products. Two of the most common fermentation processes yield methane and ethanol. Biochemical processes include those that occur naturally within the biomass. 

Some of the economic hurdles and process cost centers of this conventional carbohydrate fermentation process, schematically shown in Eigure 1, are in the complex separation steps which are needed to recover and purify the product from the cmde fermentation broths. Eurthermore, approximately a ton of gypsum, CaSO, by-product is produced and needs to be disposed of for every ton of lactic acid produced by the conventional fermentation and recovery process (30). These factors have made large-scale production by this conventional route economically and ecologically unattractive. 

Fermented Products. Fermented meat products such as semidried and dried sausages are generally recognized as safe, if critical points during processing are controlled properly. Some of the sausage processors use a small amount of fermented product as the starter for a new batch of product. 

In the 1950s, a group of coryneform bacteria which accumulate a large amount of L-glutamic acid in the culture medium were isolated (21). The use of mutant derivatives of these bacteria offered a new fermentation process for the production of many other kinds of amino acids (22). The amino acids which are produced by this method are mostiy of the T.-form, and the desired amino acid is singly accumulated. Therefore, it is very easy to isolate it from the culture broth. Rapid development of fermentative production and en2ymatic production have contributed to the lower costs of many protein amino acids and to their availabiUty in many fields as economical raw materials. 

In 1973, a multistage surface-fermentation process was patented in Japan for the production of acetic acid (42) eight surface fermenters were connected in series and arranged in such a way that the mash passed slowly through the series without disturbing the film of yAcetobacter on the surface of the medium. This equipment is reported to produce vinegar of 5% acidity and 0.22% alcohol with a mean residency time in the tanks of 22 h. 

A Chinese pubHcation (47) with 17 references reviews the use of genetically engineered microorganisms for the production of L-ascorbic acid and its precursor, 2-KGA (49). For example, a 2-keto-L-gulonic acid fermentation process from sorbose has been pubUshed with reported yields over 80% (50). 

The schemes depicted in Figure 7 contrast two complimentary approaches to cefotiam (50) in which the timing of the introduction of the C-3 substituent differs. In Route A the heterocycHc thiol C-3 substituent is introduced even before the removal of the aminoadipoyl acyl side chain. The acetonylacetyl C-3 substituent was introduced because it gave considerably higher yields and cleaner product in the nucleophilic displacement step than the corresponding acetoxy, and the starting material, deacetylcephalosporin C (5) was readily available from a fermentation process (190,191). 

Grain that is usable as food or feed is an expensive substrate for this fermentation process. A cheaper substrate might be some source of cellulose such as wood or agricultural waste. This, however, requires hydrolysis of cellulose to yield glucose. Such a process was used in Germany during World War II to produce yeast as a protein substitute. Another process for the hydrolysis of wood, developed by the U.S. Forest Products Laboratory, Madison, Wisconsin, uses mineral acid as a catalyst. This hydrolysis industry is very large in the former Soviet Union but it is not commercial elsewhere. 

Physiological Role of Citric Acid. Citric acid occurs ia the terminal oxidative metabolic system of virtually all organisms. This oxidative metabohc system (Fig. 2), variously called the Krebs cycle (for its discoverer, H. A. Krebs), the tricarboxyUc acid cycle, or the citric acid cycle, is a metaboHc cycle involving the conversion of carbohydrates, fats, or proteins to carbon dioxide and water. This cycle releases energy necessary for an organism s growth, movement, luminescence, chemosynthesis, and reproduction. The cycle also provides the carbon-containing materials from which cells synthesize amino acids and fats. Many yeasts, molds, and bacteria conduct the citric acid cycle, and can be selected for thek abiUty to maximize citric acid production in the process. This is the basis for the efficient commercial fermentation processes used today to produce citric acid. 

By-Products. The biomass from the fungal fermentation process is called mycellium and can be used as a supplement for animal feed since it contains digestable nutrients (25,26). The lime-sulfuric purification and recovery process results in large quantities of calcium sulfate cake, which is usually disposed of into a landfill but can find limited use in making plaster, cement, waUboard, or as an agricultural soil conditioner. The Hquid extraction purification and recovery process has the advantage of Htde soHd by-products. 

Fermentation Processes. The efficient production of penicillin, yeasts, and single-ceUed protein by fermentation requires defoamers to control gas evolution during the reaction. Animal fats such as lard [61789-99-9] were formerly used as a combined defoamer and nutrient, but now more effective proprietary products are usually employed. Defoamer appHcation technology has also improved. For example, in modem yeast production faciHties, the defoamers are introduced by means of automatic electrode-activated devices. One concern in the use of defoamers in fermentation processes is the potential fouHng of membranes during downstream ultrafiltration (qv). SiHcone antifoams (43,44) seem less troubled by this problem than other materials. 

Early Industrial Enzymes. Enzymes were used in ancient Greece for the production of cheese (9). Early references to this are found in Greek epic poems dating from about 800 BC. Fermentation processes for brewing, baking, and the production of alcohol have been known since prehistoric times. 

O. P. Ward, ed.. Fermentation Biotechnology Principles, Processes, Products, Vol. 1, Open University Press, Milton Keynes, 1989. 

Poly(3-hydroxybutyrate—3-hydroxyvalerate) [80181 -31 -3] resin, produced from a bacterium during a sugar fermentation process, has been reported to be biodegradable, and its target markets include "flushables" such as feminine hygiene products and disposable diapers (99). 

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