Metabolic engineering of Saccharomyces cerevisiae for the production of valencene

Sesquiterpenes and diterpenes are compounds that have commercial value in broad markets.  The total addressable market, exclusive of fuels and pharmaceuticals, has been estimated at $10–12 billion. These complex molecules are of low natural abundance and are difficult to extract or synthesize, rendering many of them very expensive and commercially inaccessible. Allylix has developed proprietary technology for the production of terpenes using synthetic biology and metabolic engineering of Saccharomyces cerevisiae.

 Naturally-occurring sesquiterpene valencene, and its oxidized form nootkatone, are high-value-added ingredients in the flavor and fragrance industry. Until recently, valencene could only be obtained by distillation of essential oils obtained from citrus fruits. Isolation of valencene from plant oils is cumbersome owing to the seasonal availability and low concentration in the fruits. The quality of the product also varies due to varying climate conditions. Using a fermentation process to make valencene, results in a sustainable, cost-effective supply of material having consistent quality.  Recently, nootkatone was also shown to be an excellent insect control agent.  The effectiveness of nootkatone for insect control has led the Centers for Disease Control to award Allylix a sole-source provider contract for the development of nootkatone as a biopesticide. 

 To produce valencene through fermentation, Allylix has isolated a novel valencene synthase. When the new enzyme was expressed in metabolically engineered high carbon flux sesquiterpene production strains, high level production of valencene was obtained. Innovative and integrated strain and fermentation process development has contributed to the cost-effective production of valencene and nootkatone at commercial scale.