Phytochemistry Reviews (v.10, #1)

Introduction by Peter Klinkhamer (1-2).

The evolution of pyrrolizidine alkaloid biosynthesis and diversity in the Senecioneae by Dorothee Langel; Dietrich Ober; Pieter B. Pelser (3-74).
Pyrrolizidine alkaloids are characteristic secondary metabolites of the Asteraceae and some other plant families. They are especially numerous and diverse in the tribe Senecioneae and form a powerful defense mechanism against herbivores. Studies into the evolution of pyrrolizidine alkaloid biosynthesis using Senecio species have identified homospermidine synthase as the enzyme responsible for the synthesis of the first specific intermediate. These studies further indicated that the homospermidine synthase-encoding gene was recruited following gene duplication of deoxyhypusine synthase and that this occurred independently in several different angiosperm lineages. A review of published pyrrolizidine alkaloid data shows that the Senecioneae are characterized by a large qualitative and quantitative variation in pyrrolizidine alkaloid profiles and that these data demonstrate little phylogenetic signal. This suggests that although the first steps of this pathway are highly conserved, the diversification of secondarily derived pyrrolizidine alkaloids is extremely plastic.
Keywords: Chemotaxonomy; Deoxyhypusine synthase; Homospermidine synthase; Secondary metabolism; Structure diversification

Pyrrolizidine alkaloids (PAs) are the major defense compounds of plants in the Senecio genus. Here I will review the effects of PAs in Senecio on the preference and performance of specialist and generalist insect herbivores. Specialist herbivores have evolved adaptation to PAs in their host plant. They can use the alkaloids as cue to find their host plant and often they sequester PAs for their own defense against predators. Generalists, on the other hand, can be deterred by PAs. PAs can also affect survival of generalist herbivores. Usually generalist insects avoid feeding on young Senecio leaves, which contain a high concentration of alkaloids. Structurally related PAs can differ in their effects on insect herbivores, some are more toxic than others. The differences in effects of PAs on specialist and generalists could lead to opposing selection on PAs, which may maintain the genetic diversity in PA concentration and composition in Senecio species.
Keywords: Evolution; Performance; Preference; Tyria jacobaeae ; Jacobaea vulgaris

Pyrrolizidine alkaloids (PAs), mainly those with a 1,2-double bond in the necine base moiety (=1,2-dehydropyrrolizidines), constitute a class of well studied compounds with respect to their flux through different trophic levels. Plants belonging to various clades (e.g. Echiteae, Eupatorieae and Senecioneae, Boraginaceae, and Crotalarieae) biosynthesize PAs as N-oxides, generally in the roots, and transport them through the phloem to stems, leaves, and reproductive structures, where they act as potent deterrents against non-specialist herbivores. On the other hand, PA specialist herbivores (mainly arctiid moths, danaine and ithomiine butterflies, and some leaf beetles) have become able to overcome this chemical barrier, and to sequester these alkaloids from their larval host plants or from sources visited by adults, such as flowers and dead or withered plants. Specialists use PAs for their own benefit as chemical defence against a vast array of predators (e.g. ants, lacewings, spiders, lizards, birds, and mammals), but some predators are able to feed on PA-insects, by avoiding or physiologically overcoming PAs present in tissues of the ingested prey. Parasitoids may be affected by PAs, depending on their degree of specialization in relation to PA-insects. Arctiidae, Danainae and Ithomiinae also use PAs as precursors of sexual pheromones. The effects of PAs on trophic interactions have been intensely studied over the last four decades, but some open questions remain, and are discussed, such as the underlying mechanisms that lead to PA diversification, activity of different PA structures, synergism among PAs and other so-called defensive substances in PA-plants, and the ability to overcome this chemical barrier by predators and parasitoids.
Keywords: Chemical defence; Insect–plant interactions; Predation; Parasitoidism; Sequestration; Sexual pheromones

A review of the phytochemical support for the shifting defence hypothesis by Leonie J. Doorduin; Klaas Vrieling (99-106).
Several theories have been developed to explain why invasive species are very successful and develop into pest species in their new area. The shifting defence hypothesis (SDH) argues that invasive plant species quickly evolve towards new defence levels in the invaded area because they lack their specialist herbivores but are still under attack by local (new) generalist herbivores. The SDH predicts that plants should increase their cheap, toxic defence compounds and lower their expensive digestibility reducing compounds. As a net result resources are saved that can be allocated to growth and reproduction giving these plants a competitive edge over the local plant species. We conducted a literature study to test whether toxic defence compounds in general are increased in the invaded area and if digestibility reducing compounds are lowered. We specifically studied the levels of pyrrolizidine alkaloids, a toxin which is known for its beneficial and detrimental impact against specialists and generalists, respectively. Digestibility reducers did not show a clear trend which might be due to the small number of studies and traits measured. The meta analysis showed that toxic compounds in general and pyrrolizidine alkaloid levels specifically, increased significantly in the invaded area, supporting the predictions of the SDH that a fast evolution takes place in the allocation towards defence.
Keywords: Defence; EICA; Invasion; PAs; SDH

The diversity of secondary metabolites (SMs) has been poorly understood from both a mechanistic and a functional perspective. Hybridization is suggested to contribute to the evolution of diversity of SMs. In this paper we discuss the effects of hybridization on SMs and herbivore resistance by evaluating the literature and with special reference to our own research results from the hybrids between Jacobaea vulgaris (syn. Senecio jacobaea) and Jacobaea aquatica (syn. Senecio aquaticus). We also review the possible genetic mechanism which causes the variation of SMs and herbivore resistance in hybrids. Most SMs in hybrids are present in the parents as well. But hybrids may miss some parental SMs or have novel SMs. The concentration of parental SMs in hybrids generally is constrained by that in parental plants, but transgressive expression was present in some hybrids. Hybrids may be as susceptible (resistant) as the parents or more susceptible than the parents, but rarely more resistant than the parents. However, different hybrid classes (F1, F2, backcrossing and mixed genotypes) show different patterns in relation to herbivore resistance. The variation in SMs and herbivore resistance occurring in hybrids could be explained by complicated genetic mechanisms rather than a simple one-gene model. Most previous work in this field only reported mean trait values for hybrid classes and few studies focused on genotype differences within hybrid classes. Our study in Jacobaea hybrids showed transgressive segregation in most SMs and herbivore resistance. To summarize, our article shows that hybridization may increase the variation of SMs and affect herbivore resistance, which may partially explain the evolution of chemical diversity in plants.
Keywords: Chemical defense; Pyrrolizidine alkaloids; Jacobaea vulgaris ; Jacobaea aquatica

The aim of this review is to combine the knowledge of studies on effects of nutrients on pyrrolizidine alkaloids (PAs) in Senecio with those studies of effects of PAs on herbivores and pathogens in order to predict the effects that nutrients may have on herbivores and pathogens via changes in PAs. We discuss whether these predictions match with the outcome of studies where the effect of nutrients on herbivores and insects were measured. PA concentrations in S. jacobaea, S. vulgaris and S. aquaticus were mostly reduced by NPK fertilization, with genotype-specific effects occurring. Plant organs varied in their response to increased fertilization; PA concentrations in flowers remained constant, while shoot and roots were mostly negatively affected. Biomass change is probably largely responsible for the change in concentrations. Nutrients affect both the variety and the levels of PAs in the plant. The reduced PA concentrations after NPK fertilization was expected to benefit herbivores, but no or negative responses from insect herbivores were observed. Apparently other changes in the plant after fertilization are overriding the effect of PAs. Pathogens do seem to benefit from the lower PA concentrations after fertilization; they were more detrimental to fertilized plants than to unfertilized control plants. Future studies should include the effect of each element of nutrients separately and in combinations in order to gain more insight in the effect of specific nutrients on PA content in Senecio plants.
Keywords: Senecio; Jacobaea; Nitrogen; Tyria; Puccinia

Defensive properties of pyrrolizidine alkaloids against microorganisms by Lotte Joosten; Johannes A. van Veen (127-136).
The understanding of the selection factors that drive chemical diversification of secondary metabolites of constitutive defence systems in plants, such as pyrrolizidine alkaloids (PAs), is still incomplete. Historically, plants always have been confronted with microorganisms. Long before herbivores existed on this planet, plants had to cope with microbial pathogens. Therefore, plant pathogenic microorganisms may have played an important role in the early evolution of the secondary metabolite diversity. In this review, we discuss the impact that plant-produced PAs have on plant-associated microorganisms. The objective of the review is to present the current knowledge on PAs with respect to anti-microbial activities, adaptation and detoxification by microorganisms, pathogenic fungi, root protection and PA induction. Many in vitro experiments showed effects of PAs on microorganisms. These results point to the potential of microorganisms to be important for the evolution of PAs. However, only a few in vivo studies have been published and support the results of the in vitro studies. In conclusion, the topics pointed out in this review need further exploration by carrying out ecological experiments and field studies.
Keywords: Anti-microbial activity; Adaptation; Pathogens; Plant defence; Secondary metabolites

Toxicity of pyrrolizidine alkaloids to humans and ruminants by Helmut Wiedenfeld; John Edgar (137-151).
1,2-dehydro pyrrolizidine ester alkaloids (PA) are toxic for human and livestock. The PAs undergo a metabolic toxication process in the liver which is the first target organ for PA poisoning. World-wide many episodes of PA intoxications have been reported involving humans as well as ruminants. This intoxication is not only related to the amount and duration of the exposure to PAs but also to species, age and gender. Besides the metabolic toxification, detoxication processes are also important. The paper discusses the toxification and detoxication processes and gives an overview about PA poisoning cases in humans and ruminants.
Keywords: Metabolic toxification; Detoxication; Poisoning in humans; Poisoning in ruminants

The ragwort species common or tansy ragwort (Jacobaea vulgaris, formerly Senecio jacobaea), marsh ragwort (S. aquaticus), Oxford ragwort (S. squalidus) and hoary ragwort (S. erucifolius) are native in Europe, but invaded North America, Australia and New Zealand as weeds. The abundance of ragwort species is increasing in west-and central Europe. Ragwort species contain different groups of secondary plant compounds defending them against generalist herbivores, contributing to their success as weeds. They are mainly known for containing pyrrolizidine alkaloids, which are toxic to grazing cattle and other livestock causing considerable losses to agricultural revenue. Consequently, control of ragwort is obligatory by law in the UK, Ireland and Australia. Commonly used management practices to control ragwort include mechanical removal, grazing, pasture management, biological control and chemical control. In this review the biology of ragwort species is shortly described and the different management practices are discussed.
Keywords: Jacobaea vulgaris ; Senecio aquaticus ; Mechanical control; Pasture management; Biological control; Chemical control