Martin Luther University Halle-Wittenberg

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The evolution of putrescine N-methyltransferase

Alkaloids like nicotine, atropine, scopolamine and their derivatives are pharmaceutically important agents used as antidotes for intoxications, for the medication of asthma, as spasmolystics, and against motion sickness. These alkaloids are formed in Solanaceae plants like Nicotiana spec. and Datura stramonium, where they are essential for protection from herbivory.

The first step in the biosynthesis of those secondary plant compounds is the methylation of the polyamine putrescine to N-methylputrescine by the enzyme putrescine N-methyltransferase (PMT). The amino acid sequence of PMT is similar to the primary metabolic enzyme spermidine synthase (SPDS), which probably represents the evolutionary precursor. As a result of amino acid changes in the course of evolution, two major changes were made in enzyme function:

  1. Cosubstrate for spermidine formation by SPDS is decarboxylated S-adenosyl-L-methionine (dcSAM) and PMT uses the cosubstrate S-adeonsyl-L-methionine (SAM) as methyl donor.
  2. SPDS accomplishes the transfer of an aminopropyl group, PMT transfers methyl groups.
Biosynthesis polyamines

Biosynthesis polyamines

Biosynthesis polyamines

That suggests the hypothesis that PMT has evolved from SPDS. To retrace possible evolutionary steps, modelling, mutagenesis, and activity assays were used to evaluate various mutants of Datura stramonium SPDS. These mutants were characterized and screened for PMT activity. After purification the mutants and PMT itself should be crystallized for X-ray analysis of the active center.

Tropan alkaloids were also found in Brassicaceae. In a further step, the possibility of PMT evolution is examined in the model plant Arabidopsis thaliana.


  • Leibniz Institute of  Plant Biochemistry Halle, PD Dr. Wolfgang Brandt
  • Martin-Luther-University Halle-Wittenberg,, Institute for Biochemics and Biotechnology, Dept. Physical Biotechnology, Prof. Dr. Milton T. Stubbs