Natural products, modification

Offen W, Martinez-Fleites C, Yang M, Kiat-Lim E, Davis BG, Tarling CA, Ford CM, Bowles DJ, Davies GJ (2006) Structure of a flavonoid glucosyltransferase reveals the basis for plant natural product modification. EMBO J 25 1396-1405... 

The second approach uses purified enzymes and in vitro reactions for target modification of compounds (Fig. 53.3). Such practice is routinely done in the laboratory, although rarely at the industrial level, for the functional characterization of biosynthetic and modifying enzymes from different sources. Moreover, such study could help to determine the exact reaction mechanisms of enzymes, the interaction between different cofactors, ligands, and other molecules with enzymes, and finally the structure of the target modifying proteins. Since this method of natural product modification requires expensive cofactors and donors, efficient enzyme activity, and optimized reaction conditions, application at the industrial... 

The appearance of the 2-(indol-3yl)ethylamine (tryptamine) unit in both tryptophan-derived natural products and in synthetic materials having potential pharmacological activity has generated a great deal of interest in the synthesis of such compounds. Several procedures which involve either direct 3-alkylation or tandem 3-functionalization/modification have been developed. Similarly, methodology applicable to preparation of tryptophan analogues has been widely explored. 

There are two main advantages of acrylamide—acryUc-based flocculants which have allowed them to dominate the market for polymeric flocculants in many appHcation areas. The first is that these polymers can be made on a commercial scale with molecular weights up to 10—15 million which is much higher than any natural product. The second is that their electrical charge in solution and the charge density can be varied over a wide range by copolymerizing acrylamide with a variety of functional monomers or by chemical modification. 

Compared to synthetic catalysts, enzymes have many advantages. First of all, being natural products, they are environmentally benign and therefore their use does not meet pubhc opposition. Enzymes act at atmospheric pressure, ambient temperature, and at pH between 4 and 9, thus avoiding extreme conditions, which might result in undesired side reactions. Enzymes are extremely selective (see below). There are also, of course, some drawbacks of biocatalysts. For example, enzymes are known in only one enantiomeric form, as they consist of natural enantiomeric (homochiral) amino acids their possible modifications are difficult to achieve (see Section 5.3.2) they are prone to deactivation owing to inappropriate operation parameters and to inhibition phenomena. 

K. S. Gates, Covalent modification of DNA by natural products, in Compre/jenxiveiVatM-ral Products Chemistry Vol. 7, (Ed. E. T. Kool), Pergamon, New York, 1999, 491. 

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