Fermentation products, commercial

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). 

There are thousands of breweries worldwide. However, the number of companies using fermentation to produce therapeutic substances and/or fine chemicals number well over 150, and those that grow microorganisms for food and feed number nearly 100. Lists of representative fermentation products produced commercially and the corresponding companies are available (1). Numerous other companies practice fermentation in some small capacity because it is often the only route to synthesize biochemical intermediates, enzymes, and many fine chemicals used in minor quantities. The large volume of L-phenylalanine is mainly used in the manufacture of the artificial dipeptide sweetener known as aspartame [22389-47-0]. Prior to the early 1980s there was httle demand for L-phenyl alanine, most of which was obtained by extraction from human hair and other nonmicrobiological sources. 

Fermentation. The commercial P-lactam antibiotics which act as starting material for all of the cephalosporins ate produced by submerged fermentation. The organisms used for the commercial production of the penicillins and cephalosporins ate mutants of PenicU/in chTysogenum and Cephalosporium acremonium respectively (3,153,154). Both ate tme fungi (eucaryotes). In contrast, the cephamycins ate produced by certain species of procaryotic Streptomyces including Streptomyces clavuligerus and Streptomyces lipmanii (21,103). 

The bacterial culture converts a portion of the supplied nutrient into vegetative cells, spores, crystalline protein toxin, soluble toxins, exoenzymes, and metabolic excretion products by the time of complete sporulation of the population. Although synchronous growth is not necessary, nearly simultaneous sporulation of the entire population is desired in order to obtain a uniform product. Depending on the manner of recovery of active material for the product, it will contain the insolubles including bacterial spores, crystals, cellular debris, and residual medium ingredients plus any soluble materials which may be carried with the fluid constituents. Diluents, vehicles, stickers, and chemical protectants, as the individual formulation procedure may dictate, are then added to the harvested fermentation products. The materials are used experimentally and commercially as dusts, wettable powders, and sprayable liquid formulations. Thus, a... 

The concept of impurity profiling is very important for antibiotics, since most of them are still produced by fermentation or by semisynthesis starting from fermentation products. Antibiotics are typically complex mixtures of several components and their composition depends on the fermentation conditions. Impurities due to degradation occur frequently. Commercial samples usually contain significant amounts of impurities with only minor structural differences among them, but differing widely in their pharmacological activities. These impurities can exhibit antibiotic activity, but in many cases they are inactive and sometimes even toxic. The applicability of CE in the analysis of antibiotics has been reviewed elsewhere. The use of CZE in impurity analysis of antibiotics is discussed in detail below. 

A number of other fermentation products have been reported to have anthelmintic activity. Among these are the aminoglycoside, G-418, the destomycins, paromomycin, anthelvencin, aspiculamycin, anthelmycin, and the axenomycins. However, none of these has seen commercial use. 

There are two commercial fungicides, the antibiotics blasticidin S and kasugamycin, that act via the inhibition of protein biosynthesis (Figure 4.19). Blasticidin S is a fermentation product obtained from cultures of Streptomyces griseochromogenes, and has specific activity in the control of P. oryzae, similar to kasugamycin, a secondary metabolite of S. kasugaensis. However, much of the earlier work on mode of action was carried out using another antibiotic, cycloheximide. 

Succinic acid is a dicarboxylic acid produced as an intermediate of the tricarboxylic acid cycle and also as one of the fermentation products of anaerobic metabolism. It has been considered an important chemical because it can be used for the precursor of 1,4-butanediol, tetrahydrofu-ran, and y-butyrolactone as well as for application in polymers, foods, pharmaceuticals, and cosmetics (1,2). Currently, succinic acid is produced commercially through chemical synthesis. However, the production of... 

The engineering of bacterial metabolic pathways to improve commercial fermentative production of amino acids has traditionally involved the use of relatively crude, nonspecific mutagenesis methods coupled to repeated rounds of arduous screening for resistance to toxic amino acid... 

The ionophores and several other specialty products are included in Table 13.8 for comparison purposes. Products of mammalian cell culture such as plasminogen activator and erythropoietin are included as fermentation products in this listing because they are normally manufactured by cellular processes in bioreactors. Aside from the five commodity chemicals in this table, the most dramatic change in the commercial chemicals produced by fermentation results from the impact of genetic engineering and recombinant DNA methods on the specialty products. Antibiotics and biopolymers (hormones, enzymes, etc.) with molecular structures too complex for conventional chemical synthesis will continue to be manufactured by microbial processes (Hinman, 1993). 

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