There are a few roadblocks to the development of kavalactones. Firstly, it is extremely difficult to cultivate outside of the tropics and takes several years to get mature. As it does not produce seeds, it can only be cultivated using cuttings which make it tough for the researchers to get a hand of great quantity of kavalactones for investigation purposes or clinical trials.
A Research by Jing-Ke Weng along with Tomáš Pluskal describes the solution to these problems and the method for creating the variants of kavalactones that are not found in nature which might prove to be more effective and safer in terms of therapeutics.
There isn’t any direct kavalactone gene. The complex metabolites such as kavalactones are made via a series of steps by using the intermediate molecules. Cells are able to combine these intermediates, then snip out a few parts of them, and add pieces onto them for creating the final molecule. So, for recreation of the kavalactone production, researchers were supposed to identify the entire pathway that the plants go through for synthesizing it.
Weng and Pluskal recognized that the kavalactones owned a similar structural backbone as of the chalcones. They hypothesized that 1 of the enzymes that was involved in the production of kavalactones had to be related to the 1 which was involved in the production of chalcones, chalcone synthase (CHS). They then looked for genes that were encoding similar enzymes and hence, found 2 synthases which had evolved from an adult CHS gene. These synthases, that they call PmSPS1 and PmSPS2, assist in shaping the basic scaffolding of the kavalactones molecules.
Once they had their kavalactone genes, they then inserted them into the bacteria and the yeast to begin the production of the molecules. This proof of the concept for their model of microbial bio-factory demonstrated that by using the microbes they could provide an efficient as well as a scalable production vehicle for the kavalactones.