Production of moth sex pheromones for pest control by yeast fermentation

Holkenbrink, C.; Ding, B.-J.; Wang, H.-L.; Dam, M. I.; Petkevicius, K.; Kildegaard, K. R.; Wenning, L.; Sinkwitz, C.; Lorantfy, B.; Koutsoumpeli, E.; Franca, L.; Pires, M.; Bernardi, C.; Urrutia, W.; Mafra-Neto, A.; Ferreira, B. S.; Raptopoulos, D.; Konstantopoulou, M.; Löfstedt, C.; Borodina, I.

doi:10.1101/2020.07.15.205047

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bioRxiv · 10.1101/2020.07.15.205047

Production of moth sex pheromones for pest control by yeast fermentation

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Abstract

The use of insect sex pheromones is an alternative technology for pest control in agriculture and forestry, which, in contrast to insecticides, does not have adverse effects on human health or environment and is efficient also against insecticide-resistant insect populations.1,2 Due to the high cost of chemically synthesized pheromones, mating disruption applications are currently primarily targeting higher value crops, such as fruits.3 Here we demonstrate a biotechnological method for the production of pheromones of economically important moth pests using engineered yeast cell factories. Biosynthetic pathways towards several pheromones or their precursors were reconstructed in the oleaginous yeast Yarrowia lipolytica, which was further metabolically engineered for improved pheromone biosynthesis by decreasing fatty alcohol degradation and downregulating storage lipid accumulation. The sex pheromone of the cotton bollworm Helicoverpa armigera was produced by oxidation of fermented fatty alcohols into corresponding aldehydes. The resulting pheromone was just as efficient and specific for trapping of H. armigera male moths in cotton fields in Greece as a synthetic pheromone mixture. We further demonstrated the production of the main pheromone component of the fall armyworm Spodoptera frugiperda. Our work describes a biotech platform for the production of commercially relevant titres of moth pheromones for pest control by yeast fermentation. Significance statementAgriculture largely relies on insecticides and genetically modified crops for pest control, however alternative solutions are required due to emerging resistance, toxicity and regulatory issues, and consumer preferences. Mating disruption with sex pheromones that act by preventing insect reproduction is considered the most promising and scalable alternative to insecticides. This method is highly efficient and safe for human health and environment. The likelihood of insect resistance development is very low and can be handled by adjusting the pheromone composition. The high cost of chemically synthesized pheromones is the major barrier for the wider adoption of pheromones. A novel method based on yeast fermentation enables the production of insect sex pheromones as a lower cost from renewable feedstocks.

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Holkenbrink, C., Ding, B.-J., Wang, H.-L., Dam, M. I., Petkevicius, K., Kildegaard, K. R., Wenning, L., Sinkwitz, C., Lorantfy, B., Koutsoumpeli, E., Franca, L., Pires, M., Bernardi, C., Urrutia, W., Mafra-Neto, A., Ferreira, B. S., Raptopoulos, D., Konstantopoulou, M., Löfstedt, C., Borodina, I.. 2020-07-16. Production of moth sex pheromones for pest control by yeast fermentation. https://doi.org/10.1101/2020.07.15.205047

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