Microbially Derived

Table 7.2 Appropriate Tm values for microbially derived viscoifiers in hard tap water (or sea waters).

Several enzymes have important therapeutic and other medical or pharmaceutical uses (Table 25.3). In this section, those enzymes used therapeutically will be described, with section 4 discnssing the applications of microbially derived enzymes for antibiotic inactivation in sterility testing and diagnostic assays. 

Whole microbial cells as well as microbially derived enzymes have played a significant role in the production of novel antibiotics. The potential of microorganisms as chemical catalysts, however, was first fully realized in the synthesis of industrially important steroids. These reactions have assumed increasing importance following the discovery that certain steroids such as hydrocortisone have anti-inflammatory activity, whilst derivatives of the steroidal sex hormones are nsefiil as oral contraceptive agents. More recently, chiral inversion of non-steroidal anti-inflammatory dmgs (NS AIDs) has been demonstrated. 

Avecia is a biotechnology company directed to the development and manufacturing of biotechnology based medicines. It is structurally organized in two business units, namely Biologies and DNA Medicines. Its capabilities comprise process development, scale-up, and manufacture of microbial-derived biopharmaceuticals and oligonucleotides. 

Microbial-derived substances secreted into the product could adversely affect the recipient s... 

Nonspecific immunostimulants (Table 9.5) can have widespread effects on the immune system similar to microbially-derived agents, including side effects akin to infection... 

CCM is considered to ameliorate the interfering effect of phytates consumed by animals, and as a result enhance Ca absorption and bioavailability. A study in chicks by Lihono et ah (1997a) directly investigated this possibility in food derived from soy beans. The effects of microbially derived phytase enzyme treatments on the bioavailability of Ca from soy-based foods fed to young male broiler chickens were examined in two separate experiments. In experiment one, the effect of phytase was tested when day-old chicks were fed com/soybean-meal-based diets, with or without 0.12% added phytase, that also included Ca from CCM (at levels 0%, 0.1%, 0.2%, and 0.3% to provide total Ca of 0.45%, 0.55%, 0.65%, and 0.75%, respectively) or Ca from CaCOs (at the 1% level, which... 

Several microbial species (in particular fungi) produce phytases (EC 3.1.3.8). The incorporation of suitable, microbially derived phytases in the diet can confer the ability to digest phytic acid on the recipient animals. This would have a threefold beneficial effect the anti-nutritional properties of phytic acid would be destroyed a lesser requirement for feed supplementation with inorganic phosphorous wottld exist and reduced phosphate levels would be present in the faeces. Several trials have confirmed that the inclusion of phytase in animal feed promotes at least some of these effects. However, the enzyme is not yet used in many cormtries. This may be explained, in part, by the fact that most microbial species only produce low levels of phytase activity which, obviously, has an effect on the cost of the finished product. It seems likely that widespread utilization of phytase within the industry will only be made possible by the production of this enzyme from recombinant sottrces, and at least two major enzyme companies are marketing such an enzyme for a nttmber of years now. 

In the late 1930s, another search was underway for microbially derived antibiotics, a quest lead by the Ukrainian immigrant to the United States, soil microbiologist Selman... 

Vitamin B12 consists of a porphyrin-like ring with a central cobalt atom attached to a nucleotide. Various organic groups may be covalently bound to the cobalt atom, forming different cobalamins. Deoxyadenosylcobalamin and methylcobalamin are the active forms of the vitamin in humans. Cyanocobalamin and hydroxocobalamin (both available for therapeutic use) and other cobalamins found in food sources are converted to the active forms. The ultimate source of vitamin Bi2 is from microbial synthesis the vitamin is not synthesized by animals or plants. The chief dietary source of vitamin Bi2 is microbially derived vitamin B12 in meat (especially liver), eggs, and dairy products. Vitamin Bi2 is sometimes called extrinsic factor to differentiate it from intrinsic factor, a protein normally secreted by the stomach that is required for gastrointestinal uptake of dietary vitamin B12. 

Microbially derived proteins mAbs from cell culture ... 

The structures of these compounds were assigned primarily by spectroscopic methods. The recrystalization of the natural Et A12-oxide (67) and the 21 -G-methyl-A12-formyl derivative of compound 63 gave single crystals and allowed X-ray analysis of these systems [74]. The absolute stereochemistry of 70 was determined by chiral GC of the L-Cys unit and by ROESY spectrum of its acetyl derivative [75]. The structures of Et s are related to the microbially derived safracins and saframycins -antitumor agents first isolated from cultured Streptomyces species [76] -as well as to the sponge metabolites renieramycin and xestomycin [77]. 

Approximately 500,000 Americans suffer strokes each year. Many of the 80% that survive suffer paralysis and impaired vision and speech, often needing rehabilitation and/or long-term care. Hence, whereas treatment using rt-PA is likely to be expensive (costs are 2200/dose for treating heat attacks), the benefits of rt-PA could outweigh costs. In the case of heart attacks, the 10 times less expensive microbially derived streptokinase can be used. There is currendy no competing pharmaceutical for treatment of strokes (18,19). Consequendy, the cost of manufacture of rt-PA may not be as dominant an issue as would be the case of other types of bioproducts. 

We found consistent differences in the fluorescence properties of fulvic acids from streams where fulvic acids are terrestrially derived and from lakes where fulvic acids are microbially derived (McKnight et al., 2001). The upper maximum in microbially derived samples is more sharply defined and... 

In the Front Range of the Rocky Mountains, the N enrichment of alpine catchments from increased atmospheric N deposition from agricultural and urban development on the plains is an important environmental and resource issue (Williams et al., 1996). The difference in N content (about 0.5-1.0% for terrestrially derived DOM vs. about 2-3% for microbially derived DOM) could be significant in terms of estimating the contribution of dissolved fulvic acid flux to the yield of N from alpine and subalpine catchments in the Rocky Mountains. The example for this alpine catchment illustrates the potential usefulness of the fluorescence index in field studies addressing applied issues related to environmental management. 

The potency of captopril (14) as an inhibitor of ACE depends critically on the configuration of the mercaptoalkanoyl moiety the compound with the S-configuration is about 100 times more active than its corresponding R-enantiomer [37], The required 3-mercapto-(25)-methylpropionic acid moiety has been prepared from microbially derived chiral 3-hydroxy-(2R)-methylpropionic acid, which is obtained by the hydroxylation of isobutyric acid [38-40],... 

Nitrilases (E.C. 3.5.5.1) promote the mild hydrolytic conversion of organonitriles directly to the corresponding carboxylic acids.19 However, less than 20 microbially derived nitrilases had been characterized at the start of this work, despite their potential synthetic value. The paucity of enzymes and the limited substrate scope of the handful of enzymes available have limited practical commercial development of nitrilase-catalyzed conversions, except in a few cases. Accordingly, we engaged in a discovery effort centered around exploiting the natural diversity available within our environmental DNA libraries and have discovered and characterized more than 200 new sequence unique nitrilases.20 All of the newly discovered nitrilases possess the conserved catalytic triad Glu-Lys-Cys that is characteristic for this enzyme class.19... 

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