Chinaberry (Melia azedarach), a mahogany species. Credit: Anna Anichkova
While colony collapse disorder, a phenomenon that occurs when the majority of worker bees in a colony disappear and leave behind a queen, peaked in 2013, the bee population is still in danger. From 2006 to 2020, commercial beekeepers in the United States reported honey bee colony loss rates averaging 30 percent each winter—compared with historical loss rates of 10 to 15 percent.
Excessive use of toxic insecticides is at least partially to blame for the world’s rapid bee decline, scientists believe. Given bees are responsible for pollinating about one-third of the world’s food supply, non-harmful insecticide alternatives are of great interest to the scientific community.
In new research, scientists at the John Innes Centre and Stanford University have taken a huge step toward that endeavor. They recently uncovered the secret of how plants make limonoids, a family of valuable organic chemicals that include bee-friendly insecticides.
Until now limonoids, a type of triterpene, could only be produced by extraction from plant material. According to researchers, their structures are too complicated to efficiently make by chemical synthesis.
For the study, published in Science, researchers used genomic tools to map the genome of Chinaberry (Melia azedarach), a mahogany species. They combined this with molecular analysis to reveal the enzymes in the biosynthetic pathway.
First, the John Innes research team mapped the genome of the plant at the chromosome-level, revealing genes encoding 10 additional enzymes that are required to produce the azadirachtin precursor, azadirone. Azadirachtin is an effective, fast-degrading, bee-friendly option for crop protection, but is not widely used due to limited supply.
Simultaneously, the team working at Stanford University was able to find 12 additional enzymes required to make khidalactone A.
“By finding the enzymes required to make limonoids, we have opened the door to an alternate production source of these valuable chemicals,” said Hannah Hodgson, co-first author of the paper and a postdoctoral scientist at the John Innes Centre.
Armed with the complete biosynthetic pathway, researchers can now produce limonoids in commonly used host plants such as Nicotiana benthamiana, vastly increasing the production of limonoids in a sustainable way. This increase in supply could then trickle down, enabling other avenues to open, such as the widespread use of azadirachtin in commercial and traditional crop protection—and the subsequent positive effect the alternative insecticide would have on the bee population.
But, the secrets of limonoids will not only protect bees. The research team says limonoid may be able to produce the anti-cancer drug candidate nimbolide. This work could enable easier access to limonoids like nimbolide to enable further study into their possible benefits. Beyond cancer, the scientists say there may be benefits of limonoids that have not even been considered yet.
“Plants make a wide variety of specialized metabolites that can be useful to humans. We are only just starting to understand how plants make complex chemicals like limonoids,” said co-corresponding author Anne Osbourn, group leader at the John Innes Centre. “Prior to this project, their biosynthesis and the enzymes involved were completely unknown, now the door is open for future research to build on this knowledge, which could benefit people in many ways.”