‘Hijacking’ core metabolism: a new panache for the evolution of steroidal glycoalkaloids structural diversity

Steroidal glycoalkaloids (SGAs) are defense specialized metabolites produced by thousands of Solanum species. These metabolites are remarkable in structural diversity formed following modifications in their core scaffold. In recent years, it became clear that a large portion of this chemical repertoire was acquired through various molecular mechanisms involving ‘hijacking’ of core metabolism enzymes. This was typically accompanied by gene duplication and divergence and further neofunctionalization as well as modified subcellular localization and evolution of new substrate preferences. In this review, we highlight recent findings in the SGAs biosynthetic pathway and elaborate on similar occurrences in other chemical classes that enabled evolution of specialized metabolic pathways and its underlying structural diversity.

Introduction

Plants are ‘natural factories’ for the production of indispensable primary metabolites and lineage-specific specialized (or secondary) metabolites. Their metabolomes are notorious for their size and structural diversity. The larger portion of this metabolic repertoire is represented by specialized metabolites, counting at least thousands in an individual plant [1]. Although more than 1 million specialized metabolites have been reported so far from plants, this represents the ‘tip of iceberg’ and counts are likely much higher. Specialized metabolites are known to play a central role in defense and abiotic stress response serving as the ‘chemical’ language for plant-environment interactions [1,2].

Steroidal glycoalkaloids (SGAs), well known as Solanum alkaloids are a major class of nitrogen-containing specialized metabolites occurring primarily in the Solanaceae and Liliaceae plant families [3]. The genus Solanum comprising more than 1350 species is the major contributing taxon for SGAs within the Solanaceae. This genus has great economic significance as it includes staple food crops such as tomato (Solanumlycopersicum), potato (Solanum tuberosum) and eggplant (Solanum melongena). In contrast, Veratrum and Fritillaria are the main genera producing steroidal alkaloids in Liliaceae [3]. Some renowned examples of these compounds are α-tomatine and dehydrotomatine in tomato, α-chaconine and α-solanine in potato, α-solamargine and α-solasonine in eggplant and cyclopamine in Veratrum species [3, 4, 5]. SGAs play a protective role in plants against a wide range of pathogens and predators, including bacteria, fungi, oomycetes, viruses, insects and animals [4,5]. In terms of their application in humans, several Solanum alkaloids are known for their anti-carcinogenic potential against the development and progression of various cancers [6]. However, some SGAs (e.g. α-solanine and α-chaconine in potato) are considered anti-nutritional compounds, and their high concentration in food is associated with toxicity, bitterness and unpleasant sensations [1,7,8]. Apart from SGAs, some noteworthy examples of anti-nutritionals in plant kingdom are cynogenic diglucosides such as amygdalin from wild almonds, oxalates and cyanides from Cassava species, glucosinolates from Brassica species and saponins from quinoa.

SGAs are distributed widely in plant tissues, including leaves, stems, roots, flowers, fruit (e.g. tomato and eggplant) and tubers (e.g. potato). In recent years, they have been extensively investigated for their occurrence, biosynthesis and diverse biological functions in tomato and potato [7, 8, 9, 10]. A typical SGA is defined by its steroidal aglycone structure and glycoside residues [11]. The steroidal aglycone is generally divided into spirosolane-type or solanidane-type (Figure 1a). The spirosolane type is the most prevalent steroidal aglycone form among the Solanaceae. On the basis of stereoisomeric subgroups, it is further subdivided into 25R-spirosolanes (e.g. solasodine in eggplant) and 25S-spirosolanes (e.g. tomatidine in tomato). The solanidane type aglycone (e.g. solanidine) is mostly restricted to domesticated and wild potato species. Lycotetraose (single d-xylose and d-galactose and two d-glucoses), solatriose (d-galactose, d-glucose and l-rhamnose), chacotriose (single d-galactose and two l-rhamnose) and commertetraose (three d-glucose and one d-galactoses) are most commonly observed glycoside moieties decorating the SGAs structure. Structures of selected SGAs based on their type of steroidal aglycone backbone and glycosylation pattern from various Solanum plants are presented in Figure 1a.

In this review, we focused on two outstanding questions related to SGAs metabolism: first, understanding how Solanum plants generate a vast repertoire of these remarkably structurally diverse class of molecules, and second, what is the evolutionary bases of these specialized metabolites biosynthetic pathway.