2-Oxoglutarate-Dependent Dioxygenases Drive Expansion of Steroidal Alkaloid Structural Diversity in the Genus Solanum

Prashant D Sonawane, Adam Jozwiak, Sayantan Panda, Bekele Abebie, Yana Kazachkova, Sachin A Gharat, Ofir Ramot, Tamar Unger, Guy Wizler, Sagit Meir, Ilana Rogachev, Adi Doron-Faigenboim, Marina Petreikov, Arthur Schaffer, Ashok P Giri, Tali Scherf, Asaph Aharoni

Research output: Contribution to journalArticlepeer-review


Solanum steroidal glycoalkaloids (SGAs) are renowned defense metabolites exhibiting spectacular structural diversity. Genes and enzymes generating SGAs precursor pathway, SGAs scaffold and glycosylated forms have been largely identified. Yet, 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 SGAs metabolism, carrying out three distinct backbone-modifying oxidative steps in addition to the three formerly reported pathway reactions. The GLYCOALKALOID METABOLISM34 (GAME34) enzyme catalyzes the conversion of core SGAs to habrochaitosides in wild tomato S. habrochaites. Cultivated tomato plants overexpressing GAME34 ectopically accumulates habrochaitosides. These habrochaitosides enriched plants extracts potently inhibits 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 α-tomatine to ripe fruit, non-bitter SGAs (e.g. esculeoside A) requires two hydroxylations; while the known GAME31 2-ODD enzyme catalyzes hydroxytomatine formation, we find that GAME40 catalyzes penultimate step in 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.
Original languageEnglish
Pages (from-to)1394-1410
Number of pages17
JournalThe New Phytologist
Issue number4
StatePublished - May 2022


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