Industry vitamin requirements

The elemental and vitamin compositions of some representative yeasts are Hsted in Table 1. The principal carbon and energy sources for yeasts are carbohydrates (usually sugars), alcohols, and organic acids, as weU as a few other specific hydrocarbons. Nitrogen is usually suppHed as ammonia, urea, amino acids or oligopeptides. The main essential mineral elements are phosphoms (suppHed as phosphoric acid), and potassium, with smaller amounts of magnesium and trace amounts of copper, zinc, and iron. These requirements are characteristic of all yeasts. The vitamin requirements, however, differ among species. Eor laboratory and many industrial cultures, a commercial yeast extract contains all the required nutrients (see also Mineral nutrients). 

Reichstein and Grbssner s second L-ascorbic acid synthesis became the basis for the industrial vitamin C production. Many chemical and technical modifications have improved the efficiency of each step, enabling this multistep synthesis to remain the principal, most economical process up to the present (ca 1997) (46). L-Ascorbic acid is produced in large, integrated, automated faciHties, involving both continuous and batch operations. The process steps are oudined in Figure 7. Procedures require ca 1.7-kg L-sorbose/kg of L-ascorbic acid with ca 66% overall yield in 1977 (55). Since 1977, further continuous improvement of each vitamin C production step has taken place. Today s overall ascorbic acid yield from L-sorbose is ca 75%. In the mid-1930s, the overall yield from L-sorbose was ca 30%. 

Cobalamln Cobalamin or vitamin Bj2 is another vitamin required for the metabolism of amino acids, fatty acids, nucleic acids, and carbohydrates. Cobalamin deficiency can cause severe and irreversible damage in the brain, nervous, cardiovascular, and hematopoietic (pernicious anemia) systems [4]. Animals, plants, and fungi do not synthesize vitamin Bj2, which can only be produced by some microorganisms. To date, the best cobalamin producer is Propionibacterium freudenreichii, which is currently applied for industrial production. 

Owing to the absence of toxicity and valuable biotechnological properties, propionic acid bacteria are widely used in industry (food industry, vitamin B]2 production). Genetic approaches may help increase strain productivity, change nutrient requirements, confer phage resistance. 

Since then Adams platinum has been used in the pharmaceutical industry and in small-scale hydrogenation reactions. When industrial processes requiring precious metal catalysts were developed it was not economic to operate with high platinum concentrations. It was, therefore, necessary to reduce costs by supporting small amounts of the metal on a suitable diluent. Supports iiKluded alumina, asbestos, sihca gel, and, most often, activated carbon. Products from these processes have included vitamins, cortisone, and dihydrostreptomycin. 

Not appropriate. Medium C would allow the growth and isolation of heterotrophs (due to the inclusion of yeast extract) and is thus not elective for methylotrophs. Also for an industrial process an organism that does not require growth factors (such as vitamins) is preferable. Medium C might well enrich for methylotrophs requring such expensive growth factors. 

The solution to the assay problem came from the fortunate finding by Mary Schorb, then working in the poultry industry, of a microorganism, Lactobacillus lactis dorner, which required vitamin B]2 for growth. With much quicker and more reliable assays the vitamin was isolated in 1948 in both the Merck and Glaxo laboratories. Its structure was determined by X-ray crystallography by Lenhert and Hodgkin (1961). 

Two things hampered efforts to isolate and purify vitamin B12 from liver first, liver contains little of this vitamin and, secondly, the assay for the activity employed the response of pernicious anemia patients. The work required processing factory quantities of liver and it is not surprising that the preparation of pure crystals of vitamin B12 took until 1948 and was accomplished nearly simultaneously in two industrial laboratories, one in the United States and one in England. 

The biomimetic-type cyclization of polyisoprenoids is an important industrial process for terpene synthesis. In most cases, a large excess of coned. H SO and SnCl. has been employed For example, ionone, a precursor of vitamin A, is prepared by coned. H2SO4 catalyzed cyclization of pseudoionone. The disadvantage of this process is undoubtedly the requirement of bases to neutralize the large excess of acid. The EGA method offers a promising alternative for this purpose. Thus, Electrolysis of 15 and 17 in a ClCHjCH Cl—LiClO —Et NClO — (Pt) system provides 16 and 18, respectively in reasonable yields and the neutralization of the reaction solution can be performed simply by addition of a small amount of pyridine... 

Many useful compounds such as amino acids, nucleic acids, alcohols, vitamins, antibiotics, foods, etc. are produced in fermentation industries. Furthermore, many organic and inorganic compounds are present in waste waters. The determination of these compounds is required for control of fermentation and environment. Analysis of these compounds can be done by spectrophotometric methods. However, complicated procedures and long reaction times are required. 

Industry response to the pressures described above—particularly the pressures for individualized medicine and for a new and more complex medical model—will be a diversification of product lines. As NDA and ANDA reviewers require more extensive testing and offer more restricted labels, industry will be forced to offer a brand extension of products. For example, look for a manufacturer of an allergy medication to introduce a variant for men, for women, for children, for older individuals, etc., much as vitamins are currently marketed. 

Acetals result from oxidative coupling of alcohols with electron-poor terminal olefins followed by a second, redox-neutral addition of alcohol [11-13]. Acrylonitrile (41) is converted to 3,3-dimethoxypropionitrile (42), an intermediate in the industrial synthesis of thiamin (vitamin Bl), by use of an alkyl nitrite oxidant [57]. A stereoselective acetalization was performed with methacrylates 43 to yield 44 with variable de [58]. Rare examples of intermolecular acetalization with nonactivated olefins are observed with chelating allyl and homoallyl amines and thioethers (45, give acetals 46) [46]. As opposed to intermolecular acetalizations, the intramolecular variety do not require activated olefins, but a suitable spatial relationship of hydroxy groups and the alkene[13]. Thus, Wacker oxidation of enediol 47 gave bicyclic acetal 48 as a precursor of a fluorinated analogue of the pheromone fron-talin[59]. 

With these reactions, a vitamin A synthesis based on acetylene was developed in the 50s, but this synthesis gained no industrial significance since the individual synthesis steps were not economically practicable. It was not possible to realise the concept aimed at, namely to link a C15 unit with a C5 building block, in the last stage. For this purpose, a reaction was required in which C—C linkage takes place with the formation of an olefmic double bond. The other double bonds are also possible linking points for the synthesis of the vitamin A molecule (2) ... 

Metabolic pathway engineering [125] is used to optimise the production of the required product based on the amount of substrate (usually biomass-derived) consumed. A so-called biobased economy is envisaged in which commodity chemicals (including biofuels), specialty chemicals such as vitamins, flavors and fragrances and industrial monomers will be produced in biorefineries (see Chapter 8 for a more detailed discussion). 

R)-pantothenic acid is an obvious candidate to be produced via fermentation, because all microorganisms synthesize the vitamin to meet their own requirements. Takeda Chemical Industries has developed a microbial partial synthesis of (R)-pantothenate in an E. coli mutant with enhanced expression of the panB, panC and panD genes [115]. High levels of (R)-pantothenate, 60 gL-1 [116], which corresponds with 30 g L-1 d-1, were obtained when 3-aminopropionate was fed to the culture. Presumably, fermentation of (R)-pantothenate with sup-pletion of 3-aminopropionate is used by Degussa in the production of Biopan . 

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