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Lactone flavors with fruity, milky, coconut, and other aromas are widely used in the food and fragrance industries. Lactones are produced by chemical synthesis or by biotransformation of plant-sourced hydroxy fatty acids. We established a novel method to produce flavor lactones from abundant non-hydroxylated fatty acids using yeast cell factories. Oleaginous yeast Yarrowia lipolytica was engineered to perform hydroxylation of fatty acids and chain-shortening via β-oxidation to preferentially twelve or ten carbons. The strains could produce γ-dodecalactone from oleic acid and δ-decalactone from linoleic acid. Through metabolic engineering, the titer was improved 4-fold, and the final strain produced 282 mg/L γ-dodecalactone in a fed-batch bioreactor. The study paves the way for the production of lactones by fermentation of abundant fatty feedstocks. • Oleaginous yeast Yarrowia lipolytica was engineered to produce flavor lactones. • The yeast expressed heterologous hydratases to obtain hydroxylated fatty acids. • β-Oxidation was engineered for preferential fatty acid chain shortening to 10/12 carbons. • γ-Dodecalactone was produced from oleic acid and δ-decalactone from linoleic acid. • γ-Dodecalactone titer reached 282 mg/L in a fed-batch process. [ABSTRACT FROM AUTHOR]

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. Due to the high cost of chemically synthesized pheromones, mating disruption applications are currently primarily targeting higher value crops, such as fruits. Here we demonstrate a biotechnological method for the production of (Z)-hexadec-11-en-1-ol and (Z)-tetradec-9-en-1-ol, using engineered yeast cell factories. These unsaturated fatty alcohols are pheromone components or the immediate precursors of pheromone components of several economically important moth pests. 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 yeast-derived pheromone was just as efficient and specific for trapping of H. armigera male moths in cotton fields in Greece as a conventionally produced synthetic pheromone mixture. We further demonstrated the production of (Z)-tetradec-9-en-1-yl acetate, the main pheromone component of the fall armyworm Spodoptera frugiperda. Taken together our work describes a biotech platform for the production of commercially relevant titres of moth pheromones for pest control via yeast fermentation. • Mating disruption with sex pheromones is an effective and safe method for pest control. • The high cost of chemically synthesized pheromones prevents their wide adoption. • Yeast Yarrowia lipolytica was engineered to produce insect pheromones and pheromone precursors. • The titer of (Z)-hexadec-11-en-1-ol in bioreactors reached 2.5 g/L. • Pheromone blend produced by oxidation of fermented fatty alcohols was effective against the cotton bollworm. [ABSTRACT FROM AUTHOR]