TY - JOUR
T1 - Incorporation of nitrogen in antinutritional Solanum alkaloid biosynthesis
AU - Grzech, Dagny
AU - Smit, Samuel J.
AU - Alam, Ryan M.
AU - Boccia, Marianna
AU - Nakamura, Yoko
AU - Hong, Benke
AU - Barbole, Ranjit
AU - Heinicke, Sarah
AU - Kunert, Maritta
AU - Seibt, Wibke
AU - Grabe, Veit
AU - Caputi, Lorenzo
AU - Lichman, Benjamin R.
AU - O’Connor, Sarah E.
AU - Aharoni, Asaph
AU - Sonawane, Prashant D.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/9/13
Y1 - 2024/9/13
N2 - Steroidal glycoalkaloids (SGAs) are specialized metabolites produced by hundreds of Solanum species including food crops, such as tomato, potato and eggplant. Unlike true alkaloids, nitrogen is introduced at a late stage of SGA biosynthesis through an unknown transamination reaction. Here, we reveal the mechanism by which GLYCOALKALOID METABOLISM12 (GAME12) directs the biosynthesis of nitrogen-containing steroidal alkaloid aglycone in Solanum. We report that GAME12, a neofunctionalized γ-aminobutyric acid (GABA) transaminase, undergoes changes in both active site specificity and subcellular localization to switch from its renown and generic activity in core metabolism to function in a specialized metabolic pathway. Moreover, overexpression of GAME12 alone in engineered S. nigrum leaves is sufficient for de novo production of nitrogen-containing SGAs. Our results highlight how hijacking a core metabolism GABA shunt enzyme is crucial in numerous Solanum species for incorporating a nitrogen to a steroidal-specialized metabolite backbone and form defensive alkaloids. (Figure presented.)
AB - Steroidal glycoalkaloids (SGAs) are specialized metabolites produced by hundreds of Solanum species including food crops, such as tomato, potato and eggplant. Unlike true alkaloids, nitrogen is introduced at a late stage of SGA biosynthesis through an unknown transamination reaction. Here, we reveal the mechanism by which GLYCOALKALOID METABOLISM12 (GAME12) directs the biosynthesis of nitrogen-containing steroidal alkaloid aglycone in Solanum. We report that GAME12, a neofunctionalized γ-aminobutyric acid (GABA) transaminase, undergoes changes in both active site specificity and subcellular localization to switch from its renown and generic activity in core metabolism to function in a specialized metabolic pathway. Moreover, overexpression of GAME12 alone in engineered S. nigrum leaves is sufficient for de novo production of nitrogen-containing SGAs. Our results highlight how hijacking a core metabolism GABA shunt enzyme is crucial in numerous Solanum species for incorporating a nitrogen to a steroidal-specialized metabolite backbone and form defensive alkaloids. (Figure presented.)
UR - http://www.scopus.com/inward/record.url?scp=85204128597&partnerID=8YFLogxK
U2 - 10.1038/s41589-024-01735-w
DO - 10.1038/s41589-024-01735-w
M3 - Article
AN - SCOPUS:85204128597
SN - 1552-4450
JO - NATURE CHEMICAL BIOLOGY
JF - NATURE CHEMICAL BIOLOGY
ER -