Vitamin B2 production

Microbial riboflavin (vitamin B2) production processes converting commodity fermentation substrates like monomeric or oligomeric carbohydrates or vegetable oils to riboflavin are the focus of the present review. The current developmental status of the riboflavin production strains derived from metabolic pathway engineering... 

Eco-efficiency demonstrated which vitamin B2 production process is the most eco-efficient. Three bio-technologicai processes and one chemical process were evaluated for the production of 100 kg of vitamin B2 for use in animal feed pre-mix. All of the processes include renewable resources such as plant oil or glucose as a raw material (Figure 3.6). The bio-technological processes use fermentation, while the chemical process starts with a bio-technological precursor like glucose or soybean oil and afterwards uses traditional chemistry to produce the vitamin B2. 

Figure 3.7 Portfolio of vitamin B2 production for the feed segment.

The water-soluble vitamins generally function as cofactors for metabolism enzymes such as those involved in the production of energy from carbohydrates and fats. Their members consist of vitamin C and vitamin B complex which include thiamine, riboflavin (vitamin B2), nicotinic acid, pyridoxine, pantothenic acid, folic acid, cobalamin (vitamin B12), inositol, and biotin. A number of recent publications have demonstrated that vitamin carriers can transport various types of water-soluble vitamins, but the carrier-mediated systems seem negligible for the membrane transport of fat-soluble vitamins such as vitamin A, D, E, and K. 

Milk is an excellent source of calcium, phosphorus, riboflavin (vitamin B2), thiamine (vitamin Bl) and vitamin B12, and a valuable source of folate, niacin, magnesium and zinc (Food Standards Agency, 2002). In particular, dairy products are an important source of calcium, which is vital for maintaining optimal bone health in humans (Prentice, 2004). The vitamins and minerals it provides are all bioavailable (i.e. available for absorption and use by the body) and thus milk consumption in humans increases the chances of achieving nutritional recommendations for daily vitamins and mineral intake (Bellew et al., 2000). 

Riboflavin is also known as vitamin B2. It contains a complex isoalloxazine ring that humans are unable to synthesize. The complex ring is hooked onto a live-carbon sugar derivative, ribitol, closely related to the ribose that occurs in RNA. The RDA for adult males is 1.3 mg/day and for adult females 1.1 mg/day. Values decrease with increasing age but increase in pregnancy and lactation. Organ meats, milk, bread products, and fortified cereals are substantial sources of riboflavin. 

More than one century ago a yellow, fluorescent pigment was isolated from whey by Blyth In the subsequent years yellow pigments were extracted from various biological materials. Depending either on the source of isolation or the physical appearance, these natural products were named e.g. lactochrome , lycochrome , ovoflavin , lactoflavin , hepatoflavin , or verdoflavin . Later, it became evident that all these compounds are riboflavin (vitamin B2). 

The economic benefits alone are also driving the adoption of biotechnology. BASF has reduced the production process for Vitamin B2 from eight steps to one through biotechnology, while DSM s bioroute for Cephalexin has also substantially reduced the number of process steps. These examples and those of dozens of pharmaceutical intermediates demonstrate that cost savings of 50 percent and more are not unlikely. The savings may come directly from lower variable costs, but also from reduced capital expenditures for simpler production assets, or from reduced scale and therefore lower risk, transportation costs, and/or overcapacity. 

This synthesis is carried out industrially for the production of vitamin B2. 

As molecules increase in complexity, the number of possibilities for mechanism of action also increase. For example, Structure 17.10 inhibits a specific kinase and specific cellular second messenger.111 In contrast, Structure 17.11 is specifically related to vitamin B2,112 while Structure 17.12, a steroid peroxide,113 is, in the imagination of this author, a molecule likely to impact steroid receptors and enzymes like cytochrome p450s involved in steroid metabolism. However, it is likely that the multiple functions observed for many complex natural products are a result of their interaction with multiple pathways and mechanisms. The environmental fates and... 

Riboflavin (vitamin B2) is an essential nutritional factor for humans (0.3-1.8 mg d-1) and animals (1-4 mg (kg diet)-1), who need it as a precursor for fla-voproteins [135]. It is produced at a volume of approx. 3 kt a-1, mainly as an animal feed additive. Approx. 300 t a-1 is used as a food additive and food colorant (E-101) and the remainder (500 t a-1) is used in pharmaceutical applications. Major producers are Roche (Switzerland), BASF (Germany), Archer-Daniels-Midland (USA) and Takeda (Japan). Microbial and chemical production have coexisted for many years but the latter has recently been phased out [136]. 

Nicotinic acid was discovered and named as a product of the chemical oxidation of nicotine in 1867. When it was later discovered to he the pellagra-preventing vitamin, it was not assigned a number among the B vitamins because its chemistry was already known. Niacin is generally placed between vitamins B2 and Bg, although it is incorrect to call it vitamin B3, which was at one time assigned to pantothenic acid (Section 12.1). 

Vitamin B complex is the collective term for a number of water-soluble vitamins found particularly in dairy products, cereals and liver.Vitamin B (thiamine) is used by mouth for dietary supplement purposes and by injection in emergency treatment of Wernicke-Korsakoff syndrome. Vitamin B2 (riboflavin) is a constituent of the coenzyme FAD (flavine adenine dinucleotide) and FMN (flavine mononucleotide) and is therefore important in cellular respiration. Vitamin Be (pyridoxine) is a coenzyme for decarboxylases and transamination, and is concerned with many metabolic processes. Overdose causes peripheral neuropathy. It may be used medically for vomiting and radiation sickness and for premenstrual tension. Pyridoxine has a negative interaction with the therapeutic use of levodopa in parkinsonism by enhancing levodopa decarboxylation to dopamine in the periphery, which does not then reach the brain. The antitubercular drug isoniazid interferes with pyridoxine, and causes a deficiency leading to peripheral neuritis that may need to be corrected with dietary supplements. Vitamin B ... 

Riboflavin, vitamin B2 (Formula 9.17), is a yellow pigment present in many products of plant and animal origin. Milk and yeast are the best sources of riboflavin. 

Although providing only comparative and not absolute values, the methodology of eco-efficiency is very useful for an evaluation of process alternatives. In Chapter 1 (Section 1.6.1), Table 1.10 summarizes the results of a study by EuropaBio to evaluate the contribution of biotechnologies to sustainability. One of the dted examples is the synthesis of vitamin B2, an essential nutrient found in meat, dairy foods, plant foods and corn products and which is required by the body to break down food components, maintain tissue and absorb other nutrients. Using the eco-efficiency and, particularly, the portfolio plot it is possible to further demonstrate the benefits... 

Despite these limitations, the eco-efficiency analysis provides a good bases for discussion. Figure 5.8 compares different alternatives, showing that, for example, the use of biomass for electricity production via the conventional combustion route is not different, in terms of eco-efficiency, with respect to biodiesel, while bioethanol is slightly worse. The best situation is for vitamin B2 by fermentation, but clearly the dimension of the market between vitamin B2 and biofuels is completely different. 

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