07 March 2016
Capturing the iridioid cyclase in action
Plants are nature’s most imaginative and diverse chemists. Being stranded in the same place, they produce a wide variety of compounds to regulate their growth and metabolism, as well as communicate with members of their species, attract pollinators or deter predators.
Most often, this variety derives from one single chemical structure, which acts as a basis for further chemical modifications that result in a compound diversity. This is the case for iridoids, where a simple 8-carbon precursor is cyclized, fused, and further modified into more complicated molecules. Iridioids have many interesting pharmacological properties, so understanding the way the plants synthetize them can facilitate large scale chemical or biotechnological production.
The biosynthesis could not happen without enzymes. Enzymes are very efficient catalysts that force chemical reactions—that would otherwise take many years—to occur in a matter of seconds, placing them within a meaningful timescale for biology. Moreover, they direct reactions in a very specific manner, allowing the production of one (or very few) of the potential chemical outcomes. As enzymes are proteins, they have a dynamic three dimensional structure. Indeed, studying this structure and capturing snapshots during catalysis has enabled biochemists to understand, improve, or alter the way an enzyme works.
This is exactly the motivation behind a work recently published in Nature Chemical Biology, titled “Structural determinants of reductive terpene cyclization in iridoid biosynthesis”, co-authored by researchers from The John Innes Centre, UK, and Fernando Geu-Flores from Copenhagen Plant Science Centre.
In this paper, the researchers crystalized the iridoid synthase of Catharanthus roseus (commonly known as rosy periwinkle), a small ornamental and medicinal plant. Using X-ray diffraction, they managed to make a 3-D model of the iridoid synthase while in action, defining the important features of the catalyst.
This work helps elucidating the catalytic mechanism used by this very important enzyme, the way the protein recognizes and binds its substrate. Refer to the original research article for more details (be warned, it contains chemistry that is not for the faint of heart).
Written by Konstantinos Vavitsas, PhD fellow in CPSC.
Edited by Lene Rasmussen, CPSC coordinator.