Alkaloids, biosynthesis examples

This chapter is an historical perspective with selected examples from our own laboratory, first at the University of Munich, and now at the Leibniz Institute of Plant Biochemistry in Halle, that reflect the changes in how we define and exploit sequence-based approaches to alkaloid biosynthesis gene identification. ... 

Figure 3.10. An example of a common feature of some types of alkaloid biosynthesis, the linking of a substance with an amino group (such as the amino acid shown here) and a substance with an aldehyde group (in this case, comprising the first stages of the route to the benzylisoquinoline alkaloids).

To try and enhance yields of speciality chemicals, attention has focused on use of plant trichomes, the glands directly producing or accumulating oils and chemicals that are typically used to protect plants from predation. Genetic and enzymic mapping of such cells has started to identify opportunities to enhance their productivity. Examples include enhancement of alkaloid biosynthesis in opium poppy trichomes (Ounaroon el al., 2003). 

Gene regulation represents the most basic level of metabolic control. Although there are few examples in the alkaloid literature, the post-translational regulation of enzymes can also exert considerable influence over the control of metabolic flux. Recent work in our laboratory suggests that enzymatic controls function of the regulation in alkaloid biosynthesis. (5)-Norcoclaurine is accepted as the central precursor to all BAs produced in plants.6,7 However, NCS was first isolated based on its ability to convert dopamine and 3,4-dihydroxyphenylacetaldehyde (3,4-DHPAA) to the tetrahydroxylated alkaloid (S)-norlaudanosoline.129 The ability of NCS to accept either 4-HPAA or 3,4-DHPAA contributed to the incorrect conclusion that (S)-norlaudanosoline is a common pathway intermediate. However, only (5)-norcoclaurine has been detected in plants. 

The production of toxins is only one aspect of plant defense strategy. As a result of the persistent battle of plants and herbivores, many optimized phenotypes have evolved, such as the preferential accumulation of alkaloids in tissues with a pattern that is consistent with predictions of optimal defense theory,65 i.e., the defense metabolites are allocated preferentially to tissues with a high probability of attack.66 The inducibility of pathways leading to plant secondary compounds as a strategy to minimize the costs of plant defense is a result of permanent optimization. One of a few examples of inducible alkaloid biosynthesis is the different Nicotiana species that exhibit dramatic wound-induced increases of nicotine, nomicotine, or anabasine.67... 

Verazine (110) has been shown to be an early intermediate in the biosynthesis of V. gvandifLovwn alkaloids, for example solanidine (75) arginine is a primary source of the nitrogen (Kaneko et al., ibid., p. 1295 1976, 25,... 

Amino acids act as precursor foe biosynthesis of alkaloids. Ornithine and lysine are common amino acids used as starting material for alkaloid biosynthesis. Cocaine and nicotine are classical examples form this series. 

The presence of some enamine, at equilibrium, is demonstrated by the conversion of piperideine into a dimer, indeed, the ability of these two systems to serve as both imines and enamines in such condensations is at the basis of their roles in alkaloid biosynthesis. Formed in nature by the oxidative deamination and decarboxylation of ornithine and lysine, they become incorporated into alkaloid structures by condensation with other precursor units. Hygrine is a simple example in which the pyrroline has condensed with ace-toacetate, or its equivalent. 

In plants the site of alkaloid biosynthesis is often separated from the site of storage for example, tropane alkaloids are produced in the root and stored in the leaves. This means that the alkaloids need to be excreted from the biosynthetically active cells and then transported to and taken up by the storage cells. In undifferentiated tissue like cells in suspension culture this transport mechanism is likely to be seriously affected this might result in low productivity. 

Alkaloids generally aeeumulate in speeifie eell types due to their eytotoxicity and probable role in plant defense responses. For example, alkaloids are sequestered to isolated idioblasts and latieifers in C. roseus (234,235), root endodermis and stem eortex or pith in T flaman (236), and latieifers in opium poppy (237). Within eells, alkaloids are often stored in diserete vesieles or the eentral vaeuole (238). The eell type- and organelle-speeifie aeeumulation of alkaloids has prompted studies on the cellular and subeellular loeahzation of the relevant biosynthetie pathways. The eell biology of alkaloid biosynthesis is remarkably diverse and eomplex (Fig. 2). 

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