Ferments, animal

Over half of all biopharmacuticals thus far approved are produced in recombinant E. coli or S. cerevisiae. Industrial-scale bacterial and yeast fermentation systems share many common features, an overview of which is provided below. Most remaining biopharmaceuticals are produced using animal cell culture, mainly by recombinant BFIK or CFiO cells (or hybridoma cells in the case of some monoclonal antibodies Appendix 1). While industrial-scale animal cell culture shares many common principles with microbial fermentation systems, it also differs in several respects, as subsequently described. Microbial fermentation/animal cell culture is a vast speciality area in its own right. As such, only a summary overview can be provided below and the interested reader is referred to the Further Reading section. 

Bhatta, R., Krishnamoorthy, U. and Mohammed, F. (2001) Effect of tamarind (Tamarindus indica) seed husk tannins on in vitro rumen fermentation. Animal Teed Science and Technology 90(3—4), 143-152. 

Doblhoff-Dier O, Unterluggauer F, Huss S, Plail R, Katinger HW (1992) Pilot scale modular hard- and software concepts for animal cell fermentation, animal cells developments, processes and products. Butterworth-Heinemann, Oxford, pp 393 - 396... 

For example, in lactate fermentation (animal cells), pyruvate is converted to lactate using the electrons of NADH, forming NAD+. Lactate is in the same oxidative state as glucose, the starting material of glycolysis. Yeast go through ethanolic fermentation for the same reason with the same result. 

Bhatta R, Krishnamoorthy U, Mohammed F (2001) Effect of tamarind Tamarindus indica) seed husktarmins on in vitro rumen fermentation. Anim Feed Sci Technol 90 143-152 Brooker JD, O Donovan LA, Skene I, Clarke K, BlackaU L, Muslera P (1994) Streptococcus caprinus sp. nov., a tannin-resistant mminal bacterium from feral goats. Lett Appl Microbiol 18 313-318... 

CastUlejos L, Calsamiglia S, Ferret A, Losa R (2005) Effects of a specific blend of essential oU compounds and the type of diet on rumen microbial fermentation and nutrient flow from a continuous culture system. Anim Feed Sci Technol 119 29-41 CastUlejos L, Calsamiglia S, Ferret A (2006) Effect of essential oils active compounds on rumen microbial fermentation and nutrient flow in in vitro systems. 1 Dairy Sci 89 2649-2658 CastUlejos L, Calsamiglia S, Ferret A, Losa R (2007) Effects of dose and adaptation time of a specific blend of essential oUs compounds on rumen fermentation. Anim Feed Sci Technol 132 186-201 Chao SC, Young DG (2000) Screening for inhibitory activity of essential oUs on selected bacteria, fungi and viruses. 1 Essent OU Res 12 639-649... 

Harfoot CG, Hazlewood GP (1988) Lipid metabolism in the rumen. In Hobson PN, Stewart CS (eds) The rumen microbial ecosystem, 2nd edn. Bladde Academic Professional, New York Hart KJ, Yanez-Ruiz DR, Duval SM, McEvan NR, Newbold CJ (2(X)8) Plant extracts to manipulate rumen fermentation. Anim Feed Sd Technol 147 8-35 Heath IB, Bauchop T, Skipp RA (1983) Assignment of the rumen anaerobe Neocallimastix frontalis to the Spizellomycetales (Chytridiomycetes) on the basis on its polyflageUate zoospore ultrastructure. Can J Bot 61 295-307... 

Newbold CJ, Wallace RJ, Watt ND, Richardson AJ (1988) The effect of the novel ionophore tetro-nasin (ICI 139603) on ruminal microorganisms. Appl Environ Microbiol 54 544-547 Newbold CJ, McIntosh FM, Williams P, Losa R, Wallace RJ (2004) Effects of a specific blend of essential oil componnds on rumen fermentation. Anim Feed Sci Technol 114 105-112 Newman DJ, Cragg GM, Snader KM (2000) The influence of natural products upon drug discovery. Nat Prod Rep 17 215-234... 

There are interesting examples of enantiomers that not only are found separately but also have different chemical properties when reacting with some reagent which is itself an enantiomer. For example (+ )-glucose is metabolized by animals and can be fermented by yeasts, but (—)-glucose has neither of these properties. The enantiomer ( + )-carvone smells of caraway whereas (—)-carvone smells of spearmint. 

Biochemistry resulted from the early elucidation of the pathway of enzymatic conversion of glucose to ethanol by yeasts and its relation to carbohydrate metaboHsm in animals. The word enzyme means "in yeast," and the earfler word ferment has an obvious connection. Partly because of the importance of wine and related products and partly because yeasts are relatively easily studied, yeasts and fermentation were important in early scientific development and stiU figure widely in studies of biochemical mechanisms, genetic control, cell characteristics, etc. Fermentation yeast was the first eukaryote to have its genome elucidated. 

PVDF-based microporous filters are in use at wineries, dairies, and electrocoating plants, as well as in water purification, biochemistry, and medical devices. Recently developed nanoselective filtration using PVDF membranes is 10 times more effective than conventional ultrafiltration (UF) for removing vimses from protein products of human or animal cell fermentations (218). PVDF protein-sequencing membranes are suitable for electroblotting procedures in protein research, or for analyzing the phosphoamino content in proteins under acidic and basic conditions or in solvents (219). 

Urethane [51-79-6] (ethyl carbamate) occurs as a natural by-product in fermented products such as wine, Hquors, yogurt, beer, bread, oHves, cheeses, and soy sauces. Whereas urethane has a known cancer etiology in experimental animals, no such relationship has yet been proven in humans (108,109). Alcohol may act by blocking the metaboHsm of urethane, and thus exert a protective effect in humans consuming alcohoHc beverages (110). 

Lactic Acid B cteri. The lactic acid bacteria are ubiquitous in nature from plant surfaces to gastrointestinal tracts of many animals. These gram-positive facultative anaerobes convert carbohydrates (qv) to lactic acid and are used extensively in the food industry, for example, for the production of yogurt, cheese, sour dough bread, etc. The sour aromatic flavor imparted upon fermentation appears to be a desirable food trait. In addition, certain species produce a variety of antibiotics. 

The therapeutically active dmg can be extracted from plant or animal tissue, or be a product of fermentation (qv), as in the case of antibiotics. Frequentiy, it is synthesized and designed to correlate stmcture with therapeutic activity. Pharmacologic activity is first tested on laboratory animals. When the results ate encouraging, physical and chemical properties are determined in the so-called preformulation stage, and analytical procedures are developed for quahty control (see Qualityassurance/qualitycontrol). 

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