Biosynthesis of natural products

Doekel, S. and Marahiel, M.A. (2001) Biosynthesis of natural products on modular peptide synthetases. Metabolic Engineering, 3 (1), 64—77. 

DFT calculations have been used to study the mechanistic pathway of the intramolecular Diels-Alder cycloaddition involved in the biosynthesis of natural products paraherquamide A and VM55599. The cycloaddition involves a dihydropyrolo[l,2- ]pyrazine as the azadiene and a standard alkene as the dienophile (Scheme 1). Analysis of the results reveals that these cycloadditions take place through concerted transition structures associated with [4+2]... 

Using this system, (Z)-hinokiresinol isolated from cultured cells of A. officinalis was determined to be the optically pure (75 )-isomer, while ( )-hinokiresinol isolated from cultured cells of C. japonica had 83.3% e.e. in favor of the (7S)-enantiomer (Table 12.1). The enzymatically formed (Z)-hinokiresinol obtained following incubation of p-coumaryl p-coumarate with a mixture of equal amounts of recZHRSa and recZHRSf) was found to be the optically pure (75)-isomer, which is identical to that isolated from A. officinalis cells (Table 12.1). A similar result was obtained with the crude plant protein from A. officinalis cultured cells, where the formed (Z)-hinokiresinol was almost optically pure, 97.2% e.e. in favor of the (75)-isomer (Table 12.1). In sharp contrast, when each subunit protein, recZHRSa or recZHRSP, was individually incubated with p-coumaryl p-coumarate, ( )-hinokiresinol was formed (Table 12.1). The enantiomeric compositions of ( )-hinokiresinol thus formed were 20.6% e.e. (with recZHRSa) and 9.0% e.e. (with recZHRSP) in favor of the (7S)-enantiomer (Table 12.1). Taken together, these results clearly indicate that the subunit composition of ZHRS controls not only cis/trans selectivity but also enantioselectivity in hinokiresinol formation (Fig. 12.3). This provides a novel example of enantiomeric control in the biosynthesis of natural products. Although the mechanism for the cis/trans selective and enantioselective reaction remains to be elucidated, for example by x-ray crystallography, the enantioselective mechanism totally differs from the enantioselectivity in biosynthesis of lignans, another class of phenylpropanoid compounds closely related to norlignans in terms of structure and biosynthesis. 

B-81MI10402 P. Manitto Biosynthesis of Natural Products , Ellis Horwood, Chichester, 1981. 109... 

Hydroxylation of aromatic rings is a very common and an important step in the biosynthesis of natural products.181,182 Arene oxides were suggested as intermediates in the biosynthesis of natural products as early as in 1967.183 However, not all hydroxylations proceed through arene oxides. A number of instances have been documented,184 as in the case of cinnamic and benzoic acids, where ortho and para hydroxylations take place by the involvement of an NIH shift (arene oxides). 

A preliminary chapter is used to outline the main building blocks and the basic construction mechanisms employed in the biosynthesis of natural products. Many of these fundamental principles... 

A Doller, A Haese, R Zocher. Molecular cloning of the amino acid activation domain of enniatin synthetase from Fusarium sambucinum. Symposium Enzymology of Biosynthesis of Natural Products, Abstract 66, Technische Universitat Berlin, September 22-25, 1996. 

Manitto, P. "Biosynthesis of Natural Products" Ellis Horwood Ltd. Chichester, England, 1981 pp. 287-429. 

Conn, E.E. (1983) Cyanogenic glucosides a possible model for the biosynthesis of natural products, in The New Frontiers in Plant Biochemistry (eds T. Akazawa, T. Ashai and H. Imaseki). Japan Scientific Societies Press, Tokyo, pp. 11-22. 

The autoxidation of hydroquinone is accompanied by the fonnation of the p-semiquinone radical this was shown as early as 1938 by Michaelis and coworkers Since then numerous additional examples of this type of reaction have been described, relating not only to hydroquinones but also to catechols, resorcinols, pyrogallols, naphthols and substituted phenols. Most of this material has been reviewed including that relating to synthetic application of phenol oxidation and to phenoxyl radicals involved in the biosynthesis of natural products -... 

The presented examples show that it is possible to assign some general rules for the introduction of stereocenters in the biosynthesis of natural products. For this, natural products need to be grouped according to their mode of biosynthesis... 

Hammerschmidt, E, Biosynthesis of natural products with a P-C bond. Part 9. Synthesis and incorporation of (5)- and (/ )-2-hydroxy[2- Hi]ethylphosphonic acid into fosfomycin by Streptomyces fradiae, Liebigs Ann. Chem., 553, 1992. 

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