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Review
. 2013 May 31;14(6):11713-41.
doi: 10.3390/ijms140611713.

Towards a molecular understanding of the biosynthesis of amaryllidaceae alkaloids in support of their expanding medical use

Adam M Takos  1 , Fred Rook
Affiliations
Review

Towards a molecular understanding of the biosynthesis of amaryllidaceae alkaloids in support of their expanding medical use

Adam M Takos et al. Int J Mol Sci. .

Abstract

The alkaloids characteristically produced by the subfamily Amaryllidoideae of the Amaryllidaceae, bulbous plant species that include well know genera such as Narcissus (daffodils) and Galanthus (snowdrops), are a source of new pharmaceutical compounds. Presently, only the Amaryllidaceae alkaloid galanthamine, an acetylcholinesterase inhibitor used to treat symptoms of Alzheimer's disease, is produced commercially as a drug from cultivated plants. However, several Amaryllidaceae alkaloids have shown great promise as anti-cancer drugs, but their further clinical development is restricted by their limited commercial availability. Amaryllidaceae species have a long history of cultivation and breeding as ornamental bulbs, and phytochemical research has focussed on the diversity in alkaloid content and composition. In contrast to the available pharmacological and phytochemical data, ecological, physiological and molecular aspects of the Amaryllidaceae and their alkaloids are much less explored and the identity of the alkaloid biosynthetic genes is presently unknown. An improved molecular understanding of Amaryllidaceae alkaloid biosynthesis would greatly benefit the rational design of breeding programs to produce cultivars optimised for the production of pharmaceutical compounds and enable biotechnology based approaches.

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Figures

Figure 1
Figure 1
Amaryllidaceae species from genera such as Galanthus (snowdrops, left) and Narcissus (daffodils, right) are popular as ornamental plants in gardens.
Figure 2
Figure 2
Chemical structures of Amaryllidaceae alkaloids mentioned in the text, illustrating some of the different subgroups.
Figure 3
Figure 3
Schematic overview of Amaryllidaceae biosynthesis. Starting from the aromatic amino acids phenylalanine and tyrosine the common precursor O-methylnorbelladine is formed. Alternative ways of oxidative phenol coupling lead to the various Amaryllidaceae alkaloid skeleton types.
Figure 4
Figure 4
Formation of (S)-norcoclaurine in the biosynthesis of benzylisoquinoline alkaloids by a Pictet-Spengler reaction. The condensation reaction between the two tyrosine derived precursors dopamine and 4-hydroxyphenylacetaldehyde is catalysed by norcoclaurine synthase (NCS).
Figure 5
Figure 5
Formation of homolycorine from norpluviine following ring opening and intramolecular rotation.
See this image and copyright information in PMC

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