4.7 Article

Tonoplast and Peroxisome Targeting of γ-tocopherol N-methyltransferase Homologs Involved in the Synthesis of Monoterpene Indole Alkaloids

Journal

PLANT AND CELL PHYSIOLOGY
Volume 63, Issue 2, Pages 200-216

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/pcp/pcab160

Keywords

Alkaloids; Catharanthus roseus; N-methyltransferase; Peroxisome; Subcellular localization; Tonoplast

Funding

  1. ARD2020 Biopharmaceutical program of the Region Centre Val de Loire (BioPROPHARM project)
  2. ARD2020 Biopharmaceutical program of the Region Centre Val de Loire (CatharSIS project)
  3. ARD2020 Biopharmaceutical program of the Region Centre Val de Loire (ETOPOCentre project)
  4. ANR MIACYC [ANR-20-CE43-0010]
  5. le STUDIUM
  6. Agence Nationale de la Recherche (ANR) [ANR-20-CE43-0010] Funding Source: Agence Nationale de la Recherche (ANR)

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Many plant species from the Apocynaceae, Loganiaceae and Rubiaceae families produce a variety of monoterpene indole alkaloids (MIAs) which have pharmacological properties. The subcellular localization of N-methyltransferases (NMTs) in MIA-producing plants adds a new layer of complexity to the biosynthetic pathway.
Many plant species from the Apocynaceae, Loganiaceae and Rubiaceae families evolved a specialized metabolism leading to the synthesis of a broad palette of monoterpene indole alkaloids (MIAs). These compounds are believed to constitute a cornerstone of the plant chemical arsenal but above all several MIAs display pharmacological properties that have been exploited for decades by humans to treat various diseases. It is established that MIAs are produced in planta due to complex biosynthetic pathways engaging a multitude of specialized enzymes but also a complex tissue and subcellular organization. In this context, N-methyltransferases (NMTs) represent an important family of enzymes indispensable for MIA biosynthesis but their characterization has always remained challenging. In particular, little is known about the subcellular localization of NMTs in MIA-producing plants. Here, we performed an extensive analysis on the subcellular localization of NMTs from four distinct medicinal plants but also experimentally validated that two putative NMTs from Catharanthus roseus exhibit NMT activity. Apart from providing unprecedented data regarding the targeting of these enzymes in planta, our results point out an additional layer of complexity to the subcellular organization of the MIA biosynthetic pathway by introducing tonoplast and peroxisome as new actors of the final steps of MIA biosynthesis.

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