@conference{
author = "Aničić, Neda and Matekalo, Dragana and Skorić, Marijana and Nestorović Živković, Jasmina and Dmitrović, Slavica and Gašić, Uroš and Dimitrijević, Milena and Anđelković, Boban and Božunović, Jelena and Milutinović, Milica and Petrović, Luka and Mišić, Danijela",
year = "2023",
abstract = "Within a large iridoids-lacking clade of Nepetoidae (Lamiaceae), the genus Nepeta stands out as an exclusive producer of these atypical monoterpenes with a unique stereochemistry. The genus Nepeta exhibits a high diversity of iridoids, with nepetalactones (NLs) predominating; however, a few Nepeta species lack these compounds. Comparative metabolomics, transcriptomics, gene co-expression, and phylogenetic analysis were conducted on the trans,cis-NL-rich N. rtanjensis Diklić & Milojević, the cis,trans-NL-dominant N. sibirica L., and the iridoid-lacking N. nervosa Royle & Bentham, revealing significant structural and functional differences in their iridoid synthases (ISY). N. rtanjensis was found to have two orthologues of ISY (NrISY1 and NrISY2), while N. sibirica and N. nervosa each had only one ISY (NsISY and NnISY, respectively). Although the phylogenetic analysis grouped NrISY1, NsISY, and NnISY with non-active Family 1 isoforms, organ-specific expression highlighted NrISY2, NsISY, and NnISY as promising ISY candidates. In vitro assays confirmed their function and NrISY2 was the most efficient in converting 8-oxogeranial to cis,trans-nepetalactol. However, 3D modeling and molecular docking analyses suggested that NnISY may have a unique cyclase activity. Likely, under in vivo conditions, the NnISY lacks substrates to catalyze, as a result of the loss of upstream geraniol synthase (GES) activity, which results in the loss of iridoids in N. nervosa. Presumably, some of the downstream pathway genes (NEPSs and MLPLs), essential for the NL biosynthesis, also underwent structural and activity changes in this species. Our ongoing work is conducted towards testing these robust hypotheses and re-establishing iridoid biosynthesis in N. nervosa.",
publisher = "Davis: University of California",
journal = "Conference Program: TERPNET 2023: The 15th International Meeting on the Biosynthesis, Function, and Synthetic Biology of Isoprenoids; 2023 Jul 31-Aug 4; Davis, USA",
title = "Functional iridoid synthases from three Nepeta species with differing iridoid profiles",
pages = "80",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6081"
}