Plants produce a vast number of structurally diverse chemicals that act on us as dangerous toxins, vitamins, or medicinal compounds. Enzymes are the biological tools used for the production of such natural products and especially those in plants are underexplored since their genes are concealed by an unusual genetic complexity. The motivation for studying the biosynthesis of plant natural products is twofold. First, the biochemical secrets hidden in the blueberries that we eat for breakfast, in the snapdragon flowers planted in our garden and in the periwinkle leaves from which cancer drugs are extracted, deserve some curiosity. Second, the enzymes performing the synthesis of a natural product can serve chemists when they are repurposed as biocatalyts in “green” chemical reactions, shuffled together in synthetic biology platforms, or even reengineered for novel reactions.
Iridoids are a natural product class present in blueberries, snapdragon, Madagascar periwinkle and thousands of other plants. Only recently, the first steps of iridoid biosynthesis have been discovered. Especially a biosynthetic step discovered in Madagascar periwinkle in the O’Connor lab, leading from a linear precursor molecule to the characteristic bicyclic core structure of iridoids, has attracted considerable attention. This step is performed by the enzyme iridoid synthase. Later in the biosynthesis, the bicyclic core is rearranged and decorated with sugars, acids or other functional groups until, in many cases, the biosynthetic origin is hardly recognizable.
We noticed unusual features in the biosynthesis of iridoids in some plants that deserved further investigation. Previous publications on the biosynthesis of some iridoids suggested a noticeable structural variation of the core scaffold. Compared to the periwinkle iridoids, the configuration of one carbon atom is attached to the opposite side of the molecule. This seemingly small structural difference indicated an iridoid synthase with opposite stereospecificity. We identified the “epi-iridoid synthase” performing this reaction and sought to understand the molecular origin of the inverted stereospecificity. Investigations of the reaction mechanism and comparisons of related iridoid synthases have challenged previous hypotheses about the function of iridoid synthases. Furthermore, some of these iridoids are converted to chlorinated derivatives. Since chlorine incorporating enzymes are generally rare in the plant kingdom and have been elusive in higher plants, we also searched for this enzyme, albeit not successfully.
