Microbes become forskolin producers
Assisting in the relaxation of human blood and respiratory vessels, forskolin could be a potent drug for treating cardiovascular problems as well as asthma and glaucoma. Meeting market needs has so far been difficult as its availability and purity depend on crop cultivation conditions. The BIOFORS (Elucidation of forskolin biosynthetic pathway in Coleus forskohlii) project has completed research on production of forskolin from microbes, a cost-effective and sustainable strategy. As a necessary step, the researchers also identified the elements of the forskolin biosynthetic cascade. Researchers found that the drug is only produced and accumulates in cells storing intracellular oil body structures within the root cork. A critical discovery, researchers identified the precursor manoyl oxide along with the assembly of enzymes necessary for its production in the oil bodies. By project end, the researchers had identified most of the enzymes involved. Two enzymes forming the backbone of the molecule and the five cytochrome P450s that catalyse oxygenations have been identified. Work is ongoing to further characterise the five enzymes as well as to identify the final enzyme required for the production of forskolin. In collaboration with an experienced biotech company, the Coleus genes responsible for forskolin production were successfully inserted into the yeast. This has resulted in high titres of deacetyl-forskolin, and lower amounts of forskolin. Further refinements such as engineering of enzymes in the pathways are necessary to improve the yield. Commercial and medicinal importance of forskolin has driven the incorporation of the forskolin biosynthetic pathway into the moss Physcomitrella patens, cyanobacteria, Escherichia coli and in tobacco chloroplast so the reaction is driven by light. The success of the BIOFORS project can be measured in terms of the number of commercial collaborators that are working with the team. Four high profile scientific journals have published the results. Moreover, four provisional patents have been filed for the pathway discovery and forskolin production in yeast.
Keywords
Microbe, forskolin, yeast, biosynthetic, enzyme, cytochrome
