Biosynthetic Products

Tsuj i and Robertson achieved the separation of neomycin B, neomycin C and neamine as the trimethylsilyl ethers on a 6ft. column of 0.75% OV-1 on Gas Chrom Q at a temperature of 290°C. The same conditions have also been shown to separate neobiosamine B, neosamine and deoxystreptamine from neomycin and neamine. Hence the method could be used to study the stability of neomycin or to monitor the biosynthetic production process. Use of the procedure to assess the stability of neomycin in pharmaceutical formulations has been demonstrated by Van Giessen and Tsuji237 with trilaurin as internal standard. However,these authors recommended a 2ft. column packed with 3%... 

Biosynthetic production of thymidine is overall a complex process combining the controlled introduction of a novel biotransformation step into a biological system with selective enhancement or knock-out of a series of existing metabolic steps. Metabolic engineering to enhance cofactor recycling at both ribonucleotide reduction and dUMP methylation steps has important parallels in other systems, as whole-cell biotransformations are frequently employed as a means to supply, in situ, high-cost and usually labile cofactors. 

These defects have spurred attempts to prepare analogs. The techniques used have been (1) natural fermentation (in which the penicillin-producing fungus is allowed to grow on a variety of complex natural nutrients from which it selects acids for incorporation into the side chain), (2) biosynthetic production (in which the fermentation medium is deliberately supplemented with unnatural precursors from which the fungus selects components for the synthesis of "unnatural" penicillins), (3) semisynthetic production (in which 6-aminopenicillanic acid (2) is obtained by a process involving fermentation, and suitably activated acids are subsequently reacted chemically with 6-APA to form penicillins with new side chains) and (4) total synthesis (potentially the most powerful method for making deep-seated structural modifications but which is at present unable to compete economically with the other methods). 

SCHEME 9. Schematic Illustration of the Biosynthesis ol Gangliosides136 by way of Transient Intermediates. (It should be noted that the biosynthetic products were identified by composition analysis and t.l.e. mobility only.)... 

Diagram showing the interrelationship of natural products, synthetics, and biosynthetic products as sources of new pharmaceuticals. 

Pettit, G.R., Herald, C.L., and Smith, C.R., Biosynthetic Products for Cancer Chemotherapy, Vol. 6, Elsevier Scientific, Amsterdam, 1989. 

The citric acid cycle is amphibolic, serving in both catabolism and anabolism cycle intermediates can be drawn off and used as the starting material for a variety of biosynthetic products. 

Despite their fascinating pharmacological properties, prostaglandins are difficult drugs to administer because, in addition to their natural scarcity, they are rapidly inactivated by enzymatic degradation and interact nonselectively with tissues and cells. Despite these difficulties, biosynthetic production of PGs has not met increasing demand. Biosyn-... 

The 5-carbon skeleton of glutamic acid gives rise directly to those of proline, ornithine, and arginine. The reactions are outlined in Fig. 24-9. Arginine, in turn, is involved in the urea cycle, which is shown in detail in Fig. 24-10. Arginine is also a biosynthetic precursor of the polyamines. Another important biosynthetic product of glutamate metabolism is 8-aminolevulinate, a precursor to porphyrins (Eq. 24-44) in some organisms.139... 

All amino acids can be degraded to C02 and water via the TCA cycle by the appropriate enzymes The pathways often contain branchpoints to useful biosynthetic products. In every case, the pathways involve the formation of a dicarboxylic acid intermediate of the TCA cycle, of pyruvate, or of acetyl-CoA. 

In 1886, A. J. Brown [11] discovered BC as a biosynthetic product of Glu-conacetobacter xylinus strains. He identified a gelatinous mass, formed on the solution during the vinegar fermentation as cellulose. In the middle of the 20th century, Hestrin and Schramm developed a special culture medium for... 

PHB and P(HB-co-HV) have several merits as matrices for controlled drug delivery [107,109]. Their biosynthetic production excludes the use of solvents, initiators, or catalysts that could, if not properly removed from the biomedical device, pose a toxicological hazard to the patient. The materials are enzymatically as well as hydrolytically degradable. Biocompatibility does not seem to be a problem the monomer D-(-)-3-hydroxybutyrate is in fact a normal constituent of blood [231]. The ease of crystallization of PHB during precipitation makes entrapment of the drug difficult [107]. Hence, copolymers with HV have been more popular for drug formulation than the pure PHB. 

In 1998, Serianni and co-workers88 again resorted to 3 mm micro-NMR probe technology in a report dealing with the detection and quantitation of the cyclic and acyclic forms of 13C-labeled aldopentoses. In a very interesting biosynthetic application, Rowe and co-workers89 investigated the conversion of <5-(L-amino-adipoyl)-L-cysteinyl-D-valine (30) to isopenicillin-N (31), an important step in the biosynthesis of penicillins and cephalosporins. The authors utilized 3 mm micro-NMR probe capabilities in their work in the analysis of the biosynthetic products of mutants of the enzyme isopenicillin-/V synthase, the enzyme normally responsible for the conversion of 30 to 31. 

Figure 10.45 Modular PKS enzymes biosynthesis of 6-deoxy erythronolide B (10.70) and modified biosynthetic products 10.71 10.73.

If one considers combinations of possible modification of the chemical structure, it may be assumed that there are more than 1000 individual structures which may occur in planta (Dinan et al, 1999). Many of the modifications found in phyfoecdysferoids are also found in ofher classes of plant triterpenoids (e.g. BRs, sterols). This fact raises the possibility that enzymes of the biosynthetic pathways may be common to plants producing these various classes of mefabolifes. A lack of specificify of fhese enzymes may cause the generation of many diverse mefabolifes or biosynthetic products without massive genetic redundancy of fhe corresponding enzymes involved. 

The opposite process occurs during biosynthesis. Simple organic molecules such as pyruvic acid, acetyl unit or intermediate compounds of citric acid cycle serve as starting molecules for varied biosynthetic products. The energy rich molecules such as ATP or NADPH derived from catabolic reactions are utilized in the biosynthetic reactions. 

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