MICROBIAL SYNTHESIS

In this process, the cofactor (NADH) is required as a source of reducing power by the enzyme involved, leucine dehydrogenase. Recycling the 

It can be seen, therefore, that biological processes (fermentation or simple enzymic transformations) can provide an environmentally friendly approach to large scale production of chiral molecules. There are, however, some drawbacks. Many processes involve aqueous conditions, some substrates deactivate the biocatalyst and therefore often products can only be accumulated at low concentration. This requires purification, which may itself produce substantial waste. 

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The modem fermentation industries developed from the early era of antibiotics. Over 4000 antibiotics have been discovered since the 1950s. However, only about 100 are produced on a commercial scale and over 40 of these are prepared by a combination of microbial synthesis and chemical modifications. Antibiotics produced by fermentation and used as starting materials in chemical syntheses are given in Table 2. 

Biosynthesis. The microbial synthesis of penicillins from eukaryotes such as C. acremonium and P. chysogenum i2iS been comprehensively... 

RA Gross. Bacterial polyesters Structural variability in microbial synthesis. In SW Shalaby, ed. Biomedical Polymers Designed-to-Degrade Systems. Cincinnati, OH Hanser/Gardner, 1994, pp 173-188. 

Biochemical and Molecular Basis of Microbial Synthesis of Polyhydroxyalkanoates in Microorganisms... 

Byrom D (1994) In Mobley DP (ed) Plastics from microbes microbial synthesis of polymers and polymer precursors. Hanser Munich, p 5... 

As an example, bulk modification by the organic reaction of unsaturated PHA with sodium permanganate resulted in the incorporation of dihydroxyl or carboxyl functional groups [106]. Due to the steric hindrance of the isotactic pendant chains, complete conversion could not be obtained. However, the solubility of the modified polymers was altered in such a way that they were now completely soluble in acetone/water and water/bicarbonate mixtures, respectively [106]. Solubility can play an important role in certain applications, for instance in hydrogels. Considering the biosynthetic pathways, the dihydroxyl or carboxyl functional groups are very difficult to incorporate by microbial synthesis and therefore organic chemistry actually has an added value to biochemistry. 

Byrom D (1994) Plastics From Microbes Microbial Synthesis of Polymers and Polymer Precursors. Hansen, New York... 

Hufford et al [57] used proton and 13C NMR spectrometric data to establish the novel sulfur-containing microbial metabolite of primaquine. Microbial metabolic studies of primaquine using Streptomyces roseochromogenus produced an A-acety-lated metabolite and a methylene-linked dimeric product, both of which have been previously reported, and a novel sulfur-containing microbial metabolite. The structure of the metabolite as an S-linked dimer was proposed on the basis of spectral and chemical data. The molecular formula C34H44N604S was established from field-desorption mass spectroscopy and analytical data. The 1H- and 13C NMR spectra data established that the novel metabolite was a symmetrical substituted dimer of primaquine A-acetate with a sulfur atom linking the two units at carbon 5. The metabolite is a mixture of stereoisomers, which can equilibrate in solution. This observation was confirmed by microbial synthesis of the metabolite from optically active primaquine. 

Shih IL, Shen MH, Van YT (2006) Microbial synthesis of poly(E-lysine) and its various applications. Bioresour Technol 97 1148-1159... 

Microbial Synthesis of Poly (3-Hydroxybutyrate-ct -4-Hydroxybutyrate) by Cupriavidus sp. USMAA1020 Isolated from Malaysian Environment... 

For the past 35 years. U.S. livestock and poultry producers have used antibiotics (products of microbial synthesis) and chemotherapeutics (chemically synthesized products). The drugs are administered in relatively large dosages to treat sick animals (therapeutically) and in lower dosages to prevent disease in exposed animals (prophylactica11 y). More commonly, small amounts... 

Thus sulfonamides are bacteriostatic drugs that inhibit bacterial growth by interfering with the microbial synthesis of folic acid. More specifically, sulfonamides block the biosynthetic pathway of folic acid synthesis, thus competitively inhibiting the transformation of p-aminobenzoic acid to folic acid (mediated by the enzyme dihydropteroate synthetase), which allows them to be considered as antimetabolites. 

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. 

B. Products under development or absolesced from microbial synthesis... 

Biosynthesis. The microbial synthesis of penicillins from eukaryotes such as C. ammonium and P. chnsogeimm has been comprehensively reviewed. In essence the biosynthesis of penicillins is described in Figure I although certain stages have yet to be fully characterized. Products are isopenicillin N, penicillin G, and penicillin N, CuHoiN O S. 

This vitamin is not synthesized in animals, but rather it results from the bacterial or fungal fermentation in the rumen, after which it is absorbed and concentrated during metabolism. Among the known vitamins, this exclusive microbial synthesis is of great interest. One of the major results of vitamin Bn deficiency is pernicious anemia. This disease, however, usually does not result from a dietary deficiency of the vitamin, but rather by an absence of a glycoprotein ( gastric intrinsic factor ) in the gastric juices that facilitates absorption of the vitamin in the intestine. Control of the diseases hence is either by injection of Bn or by oral administration of the intrinsic factor, with or without the vitamin injection. 

RN Patel, A Banerjee, L Chu, D Brzozowski, V Nanduri, LJ Szarka. Microbial synthesis of chiral intermediates for (3-3-receptor agonists. J Am Oil Chem Soc 75 1473-1488, 1998. 

However, the price of PHB-co-PHV exceeds US 10/kg, which is much higher than the cost of conventional oil-derived plastic (7). PHA yield is another major factor of the economic production of PHA. The bacterium Escherichia coli has proven to be a powerful microbial species in the microbial synthesis of bioproducts using molecular biology techniques. 

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