@article {48228,
	title = {2-oxoglutarate-dependent dioxygenases drive expansion of steroidal alkaloid structural diversity in the genus Solanum},
	journal = {New Phytologist},
	volume = {234},
	year = {2022},
	month = {MAY},
	pages = {1394-1410},
	type = {Article},
	abstract = {<p>
	Solanum steroidal glycoalkaloids (SGAs) are renowned defence metabolites exhibiting spectacular structural diversity. Genes and enzymes generating the SGA precursor pathway, SGA scaffold and glycosylated forms have been largely identified. Yet, the majority of downstream metabolic steps creating the vast repertoire of SGAs remain untapped. Here, we discovered that members of the 2-OXOGLUTARATE-DEPENDENT DIOXYGENASE (2-ODD) family play a prominent role in SGA metabolism, carrying out three distinct backbone-modifying oxidative steps in addition to the three formerly reported pathway reactions. The GLYCOALKALOID METABOLISM34 (GAME34) enzyme catalyses the conversion of core SGAs to habrochaitosides in wild tomato S. habrochaites. Cultivated tomato plants overexpressing GAME34 ectopically accumulate habrochaitosides. These habrochaitoside enriched plants extracts potently inhibit Puccinia spp. spore germination, a significant Solanaceae crops fungal pathogen. Another 2-ODD enzyme, GAME33, acts as a desaturase (via hydroxylation and E/F ring rearrangement) forming unique, yet unreported SGAs. Conversion of bitter alpha-tomatine to ripe fruit, nonbitter SGAs (e.g. esculeoside A) requires two hydroxylations; while the known GAME31 2-ODD enzyme catalyses hydroxytomatine formation, we find that GAME40 catalyses the penultimate step in the pathway and generates acetoxy-hydroxytomatine towards esculeosides accumulation. Our results highlight the significant contribution of 2-ODD enzymes to the remarkable structural diversity found in plant steroidal specialized metabolism.</p>
},
	keywords = {Solanum, specialized metabolism, steroidal glycoalkaloids (SGAs), structural diversity, Tomato},
	issn = {0028-646X},
	doi = {10.1111/nph.18064},
	author = {Sonawane, Prashant D. and Jozawiak, Adam and Barbole, Ranjit and Panda, Sayantan and Abebie, Bekele and Kazachkova, Yana and Gharat, Sachin A. and Ramot, Ofir and Unger, Tamar and Wizler, Guy and Meir, Sagit and Rogachev, Ilana and Doron-Faigenboim, Adi and Petreikov, Marina and Schaffer, Arthur and Giri, Ashok P. and Scherf, Tali and Aharoni, Asaph}
}
@article {49193,
	title = {Steroidal scaffold decorations in Solanum alkaloid biosynthesis},
	journal = {Molecular Plant},
	volume = {17},
	year = {2024},
	month = {AUG },
	pages = {1236-1254},
	type = {Article},
	abstract = {<p>
	Steroidal glycoalkaloids (SGAs) are specialized metabolites produced by hundreds of Solanum species, including important vegetable crops such as tomato, potato, and eggplant. Although it has been known that SGAs play important roles in defense in plants and {\textquoteleft}{\textquoteleft}anti-nutritional{\textquoteright}{\textquoteright}effects (e.g., toxicity and bitterness) to humans, many of these molecules have documented anti-cancer, anti-microbial, antiinflammatory, anti-viral, and anti-pyretic activities. Among these, a-solasonine and a-solamargine isolated from black nightshade (Solanum nigrum) are reported to have potent anti-tumor, anti-proliferative, and anti-inflammatory activities. Notably, a-solasonine and a-solamargine, along with the core steroidal aglycone solasodine, are the most widespread SGAs produced among the Solanum plants. However, it is still unknown how plants synthesize these bioactive steroidal molecules. Through comparative metabolomictranscriptome-guided approach, biosynthetic logic, combinatorial expression in Nicotiana benthamiana, and functional recombinant enzyme assays, here we report the discovery of 12 enzymes from S. nigrum that converts the starting cholesterol precursor to solasodine aglycone, and the downstream a-solasonine, a-solamargine, and malonyl-solamargine SGA products. We further identified six enzymes from cultivated eggplant that catalyze the production of a-solasonine, a-solamargine, and malonyl-solamargine SGAs from solasodine aglycone via glycosylation and atypical malonylation decorations. Our work provides the gene tool box and platform for engineering the production of high-value, steroidal bioactive molecules in heterologous hosts using synthetic biology.</p>
},
	keywords = {a-solamargine, Biosynthetic pathway, malonyl-solamargine, Solanum, Specialized metabolites, steroidal glycoalkaloids},
	issn = {1674-2052},
	doi = {10.1016/j.molp.2024.06.013},
	author = {Lucier, Rosalind and Kamileen, Mohamed O. and Nakamura, Yoko and Serediuk, Sofiia and Barbole, Ranjit and Wurlitzer, Jens and Kunert, Maritta and Heinicke, Sarah and O{\textquoteright}Connor, Sarah E. and Sonawane, Prashant D.}
}
