Genomic and structural basis for evolution of tropane alkaloid biosynthesis

Area of Science:

• Plant biochemistry
• Evolutionary genomics
• Medicinal chemistry

Background:

• Tropane alkaloids (TAs) like cocaine and hyoscyamine have long medicinal histories.
• Understanding the evolution of TA biosynthesis is key to their medicinal applications.

Purpose of the Study:

• To investigate the evolutionary origins of TA biosynthetic enzymes.
• To elucidate the genomic and structural basis for TA diversity and convergence.

Main Methods:

• Chromosome-level genome assembly of *Erythroxylum novogranatense* and *Anisodus acutangulus*.
• Comparative genomics, phylogenetic analysis, molecular docking, and site-directed mutagenesis.
• Synteny analysis and structural biology.

Main Results:

• Divergence in polyamine methylation due to spermidine synthase/N-methyltransferase (SPMT1) presence/absence.
• Ecgonone synthases (CYP81AN15 and CYP82M3) evolved distinct active sites for the same product.
• *CYP81AN15* arose from neofunctionalization of duplicated genes.
• Ecgonone methyltransferase evolved from salicylic acid methyltransferase via critical mutations.

Conclusions:

• TA biosynthetic enzymes evolved independently in distantly related plant species.
• Genomic and structural evidence supports independent origins and convergent evolution of TAs.
• This explains the similar medicinal properties of TAs found in diverse plant families.