Biosynthesis of the Anti‐Diabetic Metabolite Montbretin A: Glucosylation of the Central Intermediate mini‐MbA
This week we profile a recent publication in the Plant Journal from Sandra Irmisch
(pictured) in the laboratory of Dr. Jörg Bohlmann at the Michael Smith Laboratories.
Can you provide a brief overview of your lab’s current research focus?
I am working as a postdoc in the Bohlmann lab. The general focus of the lab is on important and valuable metabolites and chemicals that are found in plants. Those could be compounds which are important for the plant itself, for example chemicals that spruce trees use to defend themselves against herbivores, or compounds which are used by us humans for their flavour, fragrance or medical properties. On a broader scale we are interested in when, where, why and most importantly how plants produce these chemical compounds. If we can answer the how question, meaning identifying the enzymes that plants use to produce the compounds, we then have the opportunity to reconstruct the biosynthesis to achieve larger scale production that could be useful for drug production.
My project focuses on a compound called montbretin A (MbA). This compound is a promising new drug for the treatment of type 2 diabetes and obesity, both major problems in our society. MbA is found in the underground organs of the flowering plant montbretia (Crocosmia x crocosmiiflora). Unfortunately, the plant does not produce enough for drug development and application and the chemical structure of MbA makes it very difficult to synthesize. So we need another way to produce MbA on a larger scale. To work towards this, I am investigating how MbA is produced in the plant and what enzymes are necessary for MbA production. If we can figure out the enzymes the plant uses to produce MbA, we can reconstruct MbA biosynthesis in another system, for example yeast or tobacco by transferring those enzymes. Those systems can be easier controlled and manipulated and hopefully will allow the production of larger quantities of MbA.
What is the significance of the findings in this publication?
In our work, we investigated how MbA is produced in the montbretia plant. We uncovered the complete sequence of the MbA biosynthetic pathway and the majority of the enzymes required for the process. Using that knowledge, we were successful in recreating parts of MbA biosynthesis in tobacco plants.
What are the next steps for this research?
Up to now, we know four out of six enzymes necessary to reconstruct the complete MbA biosynthesis pathway. Two are still missing, but we are getting close to holding the complete toolbox. Once we have all the necessary enzymes, we want to produce MbA in other systems where we can more reliably attain and harvest it from. Those systems could be microbial ones like bakers yeast, or other plants like tobacco.
This work was funded by:
This research was supported with funds by the GlycoNet Networks of Centres of Excellence, and the Natural Sciences and Engineering Research Council of Canada. SI was supported by the Alexander von Humboldt foundation through a Feodor Lynen Research Fellowship.