Glycoalkaloid Biosynthesis in Solanaceous Plants

Solanaceous plants such as tomato, potato and eggplant synthesise steroidal glycoalkaloids (SGAs), a family of nitrogen‐containing metabolites that confer defence against pests and pathogens yet pose anti‐nutritional risks to consumers. Biosynthesis initiates from the mevalonate‐derived isoprenoid pathway, producing cholesterol as a core aglycone precursor. Sequential tailoring involves glycosylation, hydroxylation, acetylation and atypical malonylation steps, orchestrated by a series of specialised enzymes and regulatory proteins. Early steps convert 2,3‐oxidosqualene to cycloartenol and ultimately to cholesterol via sterol side‐chain reductases. Downstream, transaminases introduce nitrogen, dioxygenases catalyse hydroxylations that diversify defensive compounds and BAHD‐family acyltransferases finalise non‐bitter forms in ripe fruit. Spatial organisation of these enzymes, sometimes harnessed by scaffold proteins at the endoplasmic reticulum, ensures efficiency and prevents accumulation of toxic intermediates. Understanding this pathway illuminates evolutionary shifts from bitter, toxic metabolites to edible, non‐bitter fruit and offers tools for metabolic engineering of high‐value bioactive molecules and improved crop safety.

Research from Nature Portfolio

Recent studies have pinpointed key missing steps in the ripening‐associated detoxification of tomato glycoalkaloids. A BAHD‐type acyltransferase, GAME36, was shown to catalyse the acetylation that converts bitter α‐tomatine to non‐bitter Esculeoside A, completing the core pathway for ripe fruit sweetness and enabling heterologous reconstitution of Esculeoside A. In parallel, the discovery of a neofunctionalised γ-aminobutyric acid transaminase, GAME12, reveals how nitrogen is incorporated into the steroidal backbone: structural and localization changes in GAME12 drive late‐stage transamination, and its overexpression alone suffices to produce nitrogen‐containing SGAs de novo. As foundational context, a family of 2-oxoglutarate-dependent dioxygenases was identified that hydroxylate SGAs across Solanum species, enabling defence metabolite diversification and the evolution of non‐bitter downstream products in both wild and cultivated varieties.

Glycoalkaloid Biosynthesis in Solanaceous Plants publication trend

The graph below shows the total number of articles in glycoalkaloid biosynthesis in solanaceous plants across all publications each year (not limited to Nature Index journals).

Technical terms

Steroidal glycoalkaloid (SGA): A nitrogen‐containing steroidal glycoside involved in plant defence and human toxicity.

Aglycone: The non‐sugar steroidal core to which sugar moieties are attached in SGAs.

Glycosylation: Enzymatic addition of sugar residues to aglycones, crucial for SGA solubility and activity.

BAHD acyltransferase: A plant enzyme family catalysing acyl group transfer, here finalising non‐bitter SGA forms.

Transaminase: An enzyme that transfers amino groups, introducing nitrogen into specialised metabolites.

2-Oxoglutarate-dependent dioxygenase (2-ODD): An enzyme class that hydroxylates metabolites using 2-oxoglutarate and iron as cofactors.

References

1. Steroidal scaffold decorations in Solanum alkaloid biosynthesis. Molecular Plant (2024).
2. A BAHD-type acyltransferase concludes the biosynthetic pathway of non-bitter glycoalkaloids in ripe tomato fruit. Nature Communications (2023).
3. Incorporation of nitrogen in antinutritional Solanum alkaloid biosynthesis. Nature Chemical Biology (2024).
4. Development of a cascade production system finalized to the extraction of all-tomatine-rich fraction using the tomato cannery waste as feedstock. Journal of Cleaner Production (2023).
5. Sterol Side Chain Reductase 2 Is a Key Enzyme in the Biosynthesis of Cholesterol, the Common Precursor of Toxic Steroidal Glycoalkaloids in Potato. The Plant Cell (2014).
6. Pathways to defense metabolites and evading fruit bitterness in genus Solanum evolved through 2-oxoglutarate-dependent dioxygenases. Nature Communications (2019).