Vitamin fermentation process

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). 

Dlterpenes. Diterpenes contain 20 carbon atoms. The resin acids and Vitamin A are the most commercially important group of diterpenes. GibbereUic acid [77-06-5] (110), produced commercially by fermentation processes, is used as a growth promoter for plants, especially seedlings. 

Fermentation. Much time and effort has been spent in undertaking to find fermentation processes for vitamin C (47). One such approach is now practiced on an industrial scale, primarily in China. It is not certain, however, whether these processes will ultimately supplant the optimized Reichstein synthesis. One important problem is the instabiUty of ascorbic acid in water in the presence of oxygen it is thus highly unlikely that direct fermentation to ascorbic acid will be economically viable. The successful approaches to date involve fermentative preparation of an intermediate, which is then converted chemically to ascorbic acid. 

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. 

Fermentation. Fermentation is defined (Ref 3) as the production of chemicals by a series of enzyme catalyzed reactions with bacteria, yeasts, or molds under aerobic or anaerobic conditions. At present, fermentation is used to produce complex molecules not easily synthesized such as penicillin and other antibiotics, vitamin BI2, and enzymes. Formerly, glycerine (See Fetmentol), acetone, butanol, and citric lactic acids were some of the chemicals produced by fermentation process. Synthesis is now a more economical route to these materials (See also Refs 1 2) Refs 1) P.A. Wells G.E. Ward, IEC 31, 172-77(1939) 2) H.E. Silcox S.B. Lee,... 

In addition to their importance to human nutrition, vitamins are essential microbial growth factors. The significance of vitamins in winemaking is attributed to their influence on the fermentation process. 

Biotech may be gaining importance in the food and nutrition sector, but many nutritional ingredients are still produced by chemical synthesis or via extraction for example, carotenoids are currently most competitively produced by chemical means. For vitamin B2, however, the situation has changed completely in the last five years. The traditional eight-step chemical synthesis has been replaced by one fermentation process. This biotech process, which is also practiced by BASF on a large scale, reduces overall cost by up to 40 percent and the overall environmental impact by 40 percent, as has been shown by detailed life cycle assessments. Similar trends have been described for other bio-based processes, indicating that economic and environmental benefits go hand in hand in today s white biotech practice (EuropaBio and McKinsey Company, 2003, DSM position document, 2004). 

Progress in the techniques of classical strain development and metabolic engineering (Box 24) have made a growing number of fermentation processes feasible and economically attradive. Beside the bulk amino acids, lactic acid, penicillins for the pharmaceutical market, and some vitamins, for example vitamin C (ascorbic acid... 

Citric acid and vitamin C are examples of very large scale fermentation processes where the subsequent product isolation involves several bioseparations, including filtration, precipitation, evaporation, crystallization, and drying methods. The scale of operation requires careful choice of equipment which is robust, efficient in separating product from unwanted by-products, and cost effective to be competitive. 

Vitamin D2 is formed by photochemical cleavage of ergosterin, which is a side-product of many fermentation processes. Microorganisms usually contain up to 3 percent of ergosterin. 

The culture media used in fermentation processes contains a variety of unwanted cells and spores which need to be inactivated or removed before fermentation. The most commonly used inactivation method is heat sterilization. Most cells and some spores can be destroyed at60°C-80°C, while some heat-resistant spores such as bacterial spores require more than 120°C. Heat-based methods, however, cannot be used when the product molecules, such as vitamins and antibiotics, are heat sensitive, because the application of high temperatures changes their properties. In these cases, sterile filtration with membrane filters or depth filters is used. 

Historically, a classic example of an evaporation process is the production of table salt. Maple syrup has traditionally been produced by evaporation of sap. Concentration of black liquor from pulp and paper processing constitutes a large-volume present application. Evaporators are also employed in such disparate uses as desalination of seawater, nuclear fuel reprocessing, radioactive waste treatment,preparation of boiler feed waters, and production of sodium hydroxide. They are used to concentrate stillage waste in fermentation processes, waste brines, inorganic salts in fertilizer production, and rinse liquids used in metal finishing, as well as in the production of sugar, vitamin C, caustic soda, dyes, and juice concentrates, and for solvent recovery in pharmaceutical processes. 

Riboflavin (vitamin B2) can be made by fermentation, as described in U.S. 2,876,169 (to Grain Processing Corp.). The fermentation process has undergone... 

BASF s vitamin B2 process (a one-step fermentation process as opposed to an eight-step chemical synthesis) is another example of sustainable processes by bioroutes it reduces of 40% the environmental impacts and the costs. Novozymes ... 

During World War II, Glaxo became Britain s primary producer of penicillin, much as Pfizer did in the United States. By 1944 Glaxo, using Pfizer s fermentation process, had built four factories that produced 7.5 billion units, or about 80 percent of total British output. After the war, it remained Britain s leader in penicillin. At the same time, the company continued to expand its vitamin lines. Its managers then exploited this learning to enter the field of hormones by developing Britain s first commercial cortisones and then a series of corticosteroids. 

Crooke et al. (1980) discussed the fermentation process, the growth of yeast, in a continuously stirred tank fed with glucose, minerals and vitamins. Defining X as the concentration of the cells and S as that of the substrate (nutrient) a model consisting of two nonlinear differential equations of the first order was given and sustained oscillations in X and S were obtained. Specifically the cases of one limit cycle and two limit cycles were illustrated. 

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