Steroidal scaffold decorations in Solanum alkaloid biosynthesis

Area of Science:

• Plant biochemistry and synthetic biology.
• Metabolomics and molecular biology.

Background:

• Steroidal glycoalkaloids (SGAs) are plant specialized metabolites with diverse bioactivities, including anti-cancer and anti-inflammatory properties.
• Key SGAs like α-solasonine and α-solamargine, found in Solanum species, have significant therapeutic potential but their biosynthesis pathways remain largely unelucidated.
• Understanding SGA biosynthesis is crucial for harnessing their medicinal value and improving crop traits.

Purpose of the Study:

• To identify the enzymes involved in the biosynthesis of solasodine, α-solasonine, α-solamargine, and malonyl-solamargine in Solanum species.
• To establish a gene toolbox for engineering the production of valuable steroidal compounds in heterologous hosts.

Main Methods:

• Comparative metabolomic and transcriptome analysis guided the discovery of biosynthetic genes.
• Combinatorial gene expression in Nicotiana benthamiana was used to validate enzyme function.
• Functional assays of recombinant enzymes confirmed their roles in the SGA pathway.

Main Results:

• Twelve enzymes from Solanum nigrum were identified, catalyzing the conversion of cholesterol to solasodine and subsequently to α-solasonine, α-solamargine, and malonyl-solamargine.
• Six enzymes from cultivated eggplant were characterized, responsible for glycosylation and malonylation of solasodine to produce these SGAs.
• The study provides a comprehensive set of genes for SGA biosynthesis.

Conclusions:

• The identified gene toolbox enables the engineering of steroidal bioactive molecule production in synthetic biology platforms.
• This research paves the way for the scalable production of high-value SGAs for pharmaceutical and agricultural applications.
• Elucidating these pathways advances our understanding of specialized metabolism in Solanum plants.