2024-12-20 カリフォルニア大学リバーサイド校
＜関連情報＞
- https://news.ucr.edu/articles/2024/12/20/growing-safer-spuds-removing-toxins-potatoes
- https://www.science.org/doi/10.1126/science.adq5721
セルロース合成酵素様タンパク質がソラナムアルカロイドの生合成を制御する A cellulose synthase–like protein governs the biosynthesis of Solanum alkaloids
Adam Jozwiak, Sayantan Panda, Ryota Akiyama, Ayano Yoneda, […], and Asaph Aharoni
Science Published:20 Dec 2024
DOI:https://doi.org/10.1126/science.adq5721
Editor’s summary
Steroid-based natural products produced in Solanum species act as chemical defense molecules against pests and pathogens, and some also have antinutritional properties for humans. Two groups now report the identification of a cellulose synthase–like protein named GAME15 that directs the biosynthesis of these secondary metabolites. Jozwiak et al. found that GAME15 functions both as a cholesterol glucuronosyltransferase and as a scaffolding protein in a metabolon that controls cholesterol and steroidal glycoalkaloid intermediates. Boccia et al. identified the same protein and showed that deletion of the corresponding gene in Solanum nigrum produced plants lacking both steroidal alkaloids and saponins. Identification of GAME15 will pave the way to engineering the production of chemical defense molecules in heterologous plant hosts, and may aid our understanding of the balance between chemical defense and self-toxicity. —Ankit Walia
Structured Abstract
Introduction
The spatial and temporal organization of molecules is essential for orchestrating cellular metabolism because it allows for the efficient functioning of interconnected biochemical pathways. Metabolite synthesis often requires precise regulation through enzyme assemblies called metabolons, which enhance catalytic efficiency and regulate pathway flux. These complexes facilitate local substrate concentration, prevent side reactions, and protect cells from toxic intermediates. Although primary and secondary metabolic processes in plants likely rely on such enzyme assemblies, direct evidence for complex formation, particularly in those enabling substrate channeling, remains limited. Steroidal glycoalkaloids (SGAs), potent protective compounds in plants, are derived from cholesterol as the main precursor. Cholesterol is transformed through a cascade of complex reactions, yielding a multitude of structurally diverse metabolites, including well-known antinutritional compounds, such as potato alkaloids. A crucial question pertinent to many secondary metabolic pathways—extending beyond plants—is how these pathways intersect with core metabolic processes while minimizing any negative effects on overall fitness. Enzyme mappings in SGA biosynthesis reveal insights into plant strategies that sustain vitality under high demands for secondary metabolites.
Rationale
Dietary Solanaceae species, including tomato and potato, produce SGAs critical to their chemical defense. Although past studies have identified more than a dozen enzymes involved in these pathways, a comprehensive picture of SGA biosynthesis is still lacking, which presents a barrier to engineering SGAs in other hosts. Additionally, the mechanisms that coordinate the production of steroidal secondary metabolites with the constitutive accumulation of phytosterols—membrane-embedded lipids closely related to cholesterol—are still unclear. This study identifies GLYCOALKALOID METABOLISM15 (GAME15) as the so-called missing link in SGA biosynthesis. GAME15 is proposed to function as both a glucuronosyltransferase enzyme and a scaffold protein within the biosynthetic pathway, coordinating sterol metabolism and enabling the full reconstitution of SGA biosynthesis in various systems.
Results
We discovered that GAME15, a cellulose synthase–like M protein, is localized in the endoplasmic reticulum (ER) and associated with the SGA metabolic gene cluster. GAME15 catalyzes the glucuronidation of cholesterol to produce cholesterol glucuronide and serves as a scaffold to other enzymes involved in SGA biosynthesis. Functional assays conducted in Nicotiana benthamiana and yeast demonstrated that GAME15 is critical for directing metabolite flow and facilitating the efficient conversion of cholesterol to SGAs. Silencing GAME15 in tomato and potato resulted in cholesterol accumulation and a significant decrease in SGA levels, underscoring its essential role in the biosynthesis of SGAs. Protein interaction studies further revealed that GAME15 forms an enzyme complex with other biosynthetic enzymes, enhancing the transfer of intermediates along the pathway for greater metabolic efficiency.
Conclusion
GAME15 is essential for the biosynthesis of SGAs in Solanaceae plants, acting as both a glucuronosyltransferase and a scaffold protein that organizes enzyme complexes for efficient metabolic flux. The discovery of GAME15’s role in glucuronidation and its function as part of an enzyme assembly complex offers valuable insights into the evolution of complex biosynthetic pathways in plants. This knowledge presents opportunities for engineering SGA biosynthetic pathways in alternative systems, with promising applications across the food, cosmetics, and pharmaceutical industries.
