Incorporation of nitrogen in antinutritional Solanum alkaloid biosynthesis
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.
Authors
- Marianna Boccia (ORCID: https://orcid.org/0009-0008-6923-4792)
- Sarah E. O’Connor (ORCID: https://orcid.org/0000-0003-0356-6213)
- Asaph Aharoni (ORCID: https://orcid.org/0000-0002-6077-1590)
- Yoko Nakamura (ORCID: https://orcid.org/0000-0002-9622-1005)
- Veit Grabe (ORCID: https://orcid.org/0000-0002-0736-2771)
- Benjamin R. Lichman (ORCID: https://orcid.org/0000-0002-0033-1120)
- Dagny Grzech (ORCID: https://orcid.org/0000-0001-5575-2582)
- Ranjit S. Barbole (ORCID: https://orcid.org/0000-0001-5265-512X)
- Lorenzo Caputi (ORCID: https://orcid.org/0000-0002-7783-6733)
- Samuel J. Smit (ORCID: https://orcid.org/0000-0002-7382-5113)
- Ryan M. Alam (ORCID: https://orcid.org/0000-0002-0227-0771)
- Sarah Heinicke
- Prashant D. Sonawane (ORCID: https://orcid.org/0000-0002-3631-1703)
- Benke Hong (ORCID: https://orcid.org/0009-0000-7557-8278)
- Maritta Kunert
- Wibke Seibt
Institutions
- Max Planck Institute for Chemical Ecology (DE)
- University of York (GB)
- Weizmann Institute of Science (IL)
Publication Details
- Journal
- Nature Chemical Biology
- Published
- 2024-09-13
- DOI
- https://doi.org/10.1038/s41589-024-01735-w
- Citations
- 21
- Primary Topic
- Potato Plant Research
- Type
- article
- Field-Weighted Citation Impact
- 7.32
Funders
- Leona M. and Harry B. Helmsley Charitable Trust
- UK Research and Innovation
- Weizmann Institute of Science
- Max-Planck-Gesellschaft
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council