Pyrrolizidine Alkaloids: Biosynthesis, Biological Activities and Occurrence in Crop Plants

Abstract

Pyrrolizidine alkaloids (PAs) are heterocyclic secondary metabolites with a typical pyrrolizidine motif predominantly produced by plants as defense chemicals against herbivores. They display a wide structural diversity and occur in a vast number of species with novel structures and occurrences continuously being discovered. These alkaloids exhibit strong hepatotoxic, genotoxic, cytotoxic, tumorigenic, and neurotoxic activities, and thereby pose a serious threat to the health of humans since they are known contaminants of foods including grain, milk, honey, and eggs, as well as plant derived pharmaceuticals and food supplements. Livestock and fodder can be affected due to PA-containing plants on pastures and fields. Despite their importance as toxic contaminants of agricultural products, there is limited knowledge about their biosynthesis. While the intermediates were well defined by feeding experiments, only one enzyme involved in PA biosynthesis has been characterized so far, the homospermidine synthase catalyzing the first committed step in PA biosynthesis. This review gives an overview about structural diversity of PAs, biosynthetic pathways of necine base, and necic acid formation and how PA accumulation is regulated. Furthermore, we discuss their role in plant ecology and their modes of toxicity towards humans and animals. Finally, several examples of PA-producing crop plants are discussed.

The scaffold-forming steps of plant alkaloid biosynthesis

“…There have been many excellent general reviews of alkaloids, 16,17,19 and many detailed reviews of individual alkaloid families. 14,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] In order to differentiate this review, and to highlight its focus on the patterns in the early steps of biosynthesis, it will not be structured by alkaloid class but instead by the particular step in the aforementioned biosynthetic model (Scheme 1). By viewing alkaloid biosynthesis in this holistic manner, it may be possible to gain insights from one pathway that can be applied to aid elucidation of another.…”

Molecular evolution of gland cell types and chemical interactions in animals

“…Another is non-enzymatic reactivity, which occurs spontaneously as a result of physicochemical properties of molecules. Examples are the intramolecular formation of Schiff bases, and the intra-and intermolecular Mannich reactions in alkaloid biosynthesis (Dewick, 2002;Leete, 1967;Schramm et al, 2019). A further phenomenon is the presence or absence of bacterial symbionts that may mediate reactions either inside the gland or elsewhere by modifying precursors (Becerra et al, 2015;Brucker et al, 2008;Florez et al, 2015;Piel, 2002;Piel et al, 2004).…”

Discriminant analysis of pyrrolizidine alkaloid contamination in bee pollen based on near-infrared data from lab-stationary and portable spectrometers

“…Indeed, both the PA/PANO concentration and composition depend on the botanical taxon, geographical origin [35] and developmental stage of the plants. Moreover, synthesis of PAs/ PANOs by plants is influenced by many other agronomic and environmental factors such as soil fertility, water availability and climate conditions [36][37][38]. Since most bee pollen samples analysed were from Italy and other European countries, possible sources of the lycopsaminetype PAs/PANOs could be plants from the genus Echium (e.g., E. vulgare), which is known to produce high levels of echimidine and its N-oxide, and Borago officinalis and Eupatorium cannabinum that synthesise lycopsamine, lycopsamine N-oxide and their isomers.…”