Incorporation of nitrogen in antinutritional Solanum alkaloid biosynthesis

Dagny Grzech; Samuel J. Smit; Ryan M. Alam; Marianna Boccia; Yoko Nakamura; Benke Hong; Ranjit Barbole; Sarah Heinicke; Maritta Kunert; Wibke Seibt; Veit Grabe; Lorenzo Caputi; Benjamin R. Lichman; Sarah E. O’Connor; Asaph Aharoni; Prashant D. Sonawane

doi:10.1038/s41589-024-01735-w

Incorporation of nitrogen in antinutritional Solanum alkaloid biosynthesis

Dagny Grzech, Samuel J. Smit, Ryan M. Alam, Marianna Boccia, Yoko Nakamura, Benke Hong, Ranjit Barbole, Sarah Heinicke, Maritta Kunert, Wibke Seibt, Veit Grabe, Lorenzo Caputi, Benjamin R. Lichman, Sarah E. O’Connor, Asaph Aharoni, Prashant D. Sonawane

Department of Plant and Environmental Sciences

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

Abstract

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.)

Original language	English
Article number	25
Pages (from-to)	131-142
Number of pages	27
Journal	Nature Chemical Biology
Volume	21
Issue number	1
DOIs	https://doi.org/10.1038/s41589-024-01735-w
State	Published Online - 13 Sep 2024

All Science Journal Classification (ASJC) codes

Molecular Biology
Cell Biology

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Grzech, D., Smit, S. J., Alam, R. M., Boccia, M., Nakamura, Y., Hong, B., Barbole, R., Heinicke, S., Kunert, M., Seibt, W., Grabe, V., Caputi, L., Lichman, B. R., O’Connor, S. E., Aharoni, A., & Sonawane, P. D. (2024). Incorporation of nitrogen in antinutritional Solanum alkaloid biosynthesis. Nature Chemical Biology, 21(1), 131-142. Article 25. Advance online publication. https://doi.org/10.1038/s41589-024-01735-w

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title = "Incorporation of nitrogen in antinutritional Solanum alkaloid biosynthesis",

abstract = "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.)",

author = "Dagny Grzech and Smit, {Samuel J.} and Alam, {Ryan M.} and Marianna Boccia and Yoko Nakamura and Benke Hong and Ranjit Barbole and Sarah Heinicke and Maritta Kunert and Wibke Seibt and Veit Grabe and Lorenzo Caputi and Lichman, {Benjamin R.} and O{\textquoteright}Connor, {Sarah E.} and Asaph Aharoni and Sonawane, {Prashant D.}",

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doi = "10.1038/s41589-024-01735-w",

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Grzech, D, Smit, SJ, Alam, RM, Boccia, M, Nakamura, Y, Hong, B, Barbole, R, Heinicke, S, Kunert, M, Seibt, W, Grabe, V, Caputi, L, Lichman, BR, O’Connor, SE, Aharoni, A & Sonawane, PD 2024, 'Incorporation of nitrogen in antinutritional Solanum alkaloid biosynthesis', Nature Chemical Biology, vol. 21, no. 1, 25, pp. 131-142. https://doi.org/10.1038/s41589-024-01735-w

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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.

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.)

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DO - 10.1038/s41589-024-01735-w

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SN - 1552-4450

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JO - Nature Chemical Biology

JF - Nature Chemical Biology

IS - 1

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ER -

Incorporation of nitrogen in antinutritional Solanum alkaloid biosynthesis

Abstract

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