Secondary metabolites transformation

In 1992, Paul and Van Alstyne reported on the processes that occur after tissue disruption in different species of the calcified green seaweed Halimeda [56]. After wounding, these algae transform their major secondary metabolite, the his-enoylacetate diterpene halimedatetraacetate (48), into halimedatrial (50) and epihalimedatrial (51). The structural relationship between the educt and the reaction products suggests that the transformation occurs by a combination of solvolysis and hydrolysis reactions as indicated in Scheme 14 [108]. 

The presence in molluscs of molecules structurally related to typical dietary metabolites could be ascribed either to selective accumulation of minor compounds acquired through the diet, or to an in vivo chemical transformation of major metabolites acquired from the prey. However, all reports on this topic have to be carefully evaluated before drawing hurried conclusions. In particular, interaction among molecules from different organs could favor formation of artifacts when the secondary metabolites are extracted from the whole mollusc and not from individual dissected tissues. Only some cases, where the ability of the molluscs to modify dietary metabolites seems to be well supported, are reported in this chapter. 

Aryl side chain containing L-a-amino acids, such as phenylalanine (Phe), tyrosine (Tyr), and tryptophan (Trp), are derived through the shikimate pathway. The enzymatic transformation of phosphoenolpyr-uvate (PEP) and erythro-4-phosphate, through a series of reactions, yields shikimate (Scheme 2). Although shikimate is an important biosynthetic intermediate for a number of secondary metabolites, this chapter only describes the conversion of shikimate to amino acids containing aryl side chains. In the second part of the biosynthesis, shikimate is converted into chorismate by the addition of PEP to the hydroxyl group at the C5 position. Chorismate is then transformed into prephenate by the enzyme chorismate mutase (Scheme 3). 

On the other hand, some compounds which are Included may not be true Gossypium secondary metabolites. Not only are the sources mentioned above possible contributors of exogenous compounds which have been Included in the accompanying Tables (I - X), but also it is quite possible that methods of isolation and analysis caused molecular transformation which created Isomers of true metabolites or even caused more drastic alterations. The diversity of structures which are plausible natural products is so great that it is not reasonable to exclude many of those reported simply on the basis of structure assignment. For this reason, it can be expected that some errors of inclusion have been made. 

Metabolic transformations are characterized by high speed and yield, as well as high regio-, diastereo-and enantio-specificity. Errors in the stereochemistry of the molecules that serve to construct the genetic material are smaller than for the planetary motions. With secondary metabolites, however, enantiomerically inq)ure con unds are also encoimtered, typkally with monoterpenes and alkaloids from terrestrial plants even ant dal pathways in the same organism have been found, albeit as rare events (Guella 1998). 

Plants are known as a potential source of a large number of important biochemical constituents (1-3). In recent years, transformed hairy roots have been studied as a potential large-scale source for production of plant-derived useful compounds such as pharmaceuticals. They have several advantages compared to plant cell suspension culture, such as high growth rate, high and stable secondary metabolite productivity, autotrophy of... 

Molluscs can be divided into two biosynthetic categories based on the chemistry they exhibit relative to their diet those that are dependent on dietary sources express chemistry that reflects their choice of diet. In some instances, molluscs have been shown to chemically modify the ingested compounds. These transformations may either enhance the deterrent nature of the metabolite or alternatively represent a detoxification mechanism examples of both are documented below. The second category of molluscs are those which have the ability to biosynthesize metabolites de novo and, hence, may sometimes express a preference for a diet lacking secondary metabolites. The expense of maintaining secondary metabolic function is balanced against the lack of dietary constraints. Molluscs that can produce their own defensive allomones are likely to have an advantage over those dependent on a dietary source of metabolites. 

Secondary metabolites can accumulate in the same cell and tissue in which they are formed, but intermediates and end-products can also be transported to other locations for further elaboration or accumulation. For example, TAs and nicotine are typically produced near the root apex, but mostly accumulate within leaf cell vacuoles. Even TA biosynthesis itself involves intercellular transport of several pathway intermediates (Fig.7.9A). P-Glucuronidase (GUS) localization in A. belladonna roots transformed with a PMT promoter-GUS fusion showed that PMT expression is restricted to the pericycle.144 Immunolocalization and in situ RNA hybridization also demonstrated the pericycle-specific expression of H6H.145,146 In contrast, TR-I was immunolocalized to the endodermis and outer root cortex, whereas TR-II was found in the pericycle, endodermis, and outer cortex.85 The localization of TR-I to a different cell type than PMT and H6H implies that an intermediate between PMT and TR-I moves from the pericycle to the endodermis (Fig.7.9A). Similarly, an intermediate between TR-I and H6H must move back to the pericycle. The occurrence of PMT in the pericycle provides the enzyme with efficient access to putrescine, ornithine, and arginine unloaded from the phloem. In the same way, scopolamine produced in the pericycle can be readily translocated to the leaves via the adjacent xylem. 

The precursor analysis approach should now be seen as a useful complement to traditional methods of flavor analysis of fruits. The latter methods are often limited to the painstaking processes of isolation and identification of those trace constituents which are directly responsible for flavor. The precursor analysis approach takes advantage of the evidence provided by Nature vhen secondary metabolites, including flavor corpounds, are biochanically transformed and accumulated by the fruit. 

Dehydrothyrsiferol (3), an analogue of thyrsiferol (1), was the next marine metabolite discovered from Laurencia. In an effort to assess halogen-based secondary metabolite synthesis, Norte and co-workers isolated compound 3 in 1984 as a white crystalline solid [6]. This natural product was found in Laurencia pinnatifida located on the Cannary Islands of Spain. Its chemical structure was verified via chemical transformation into thyrsiferol (1). 

A number of different methods for stable or transient genetic transformation of plants or plant cells have been developed [13-15]. These comprise particle bombardment, Agro actermm-mediated transformation, floral dip transformation, agrodrench, viral vectors, protoplast transformation and ultrasound. These are the main techniques for the genetic transformation of plants, and many of them have also been applied for the transformation of secondary metabolite pathways in an attempt to alter the metabolic pathways of target... 

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