Fatty alcohols are important industrial oleochemicals with broad applications and a growing market. As such, we sought to engineer Yarrowia lipolytica to serve as a renewable source of fatty alcohols (specifically hexadecanol, heptadecanol, octadecanol, oleyl alcohol) directly from glucose. Through screening four fatty acyl-CoA reductase (FAR) enzyme variants across two engineered background strains, we identified that the previously characterized MhFAR enabled the highest production. The use of two strains demonstrated the close relationship between the fatty acid distribution and corresponding fatty alcohol production profile. Strain engineering, fed-batch flask cultivation, and dodecane extractive fermentation improved the fatty alcohol titer to 1.5 g/L. Scale-up of this strain in a (non-extractive) 2L bioreactor led to 5.8 g/L total fatty alcohols at an average yield of 36 mg/g glucose with a maximum productivity of 39 mg/L hr. These parameters represent the highest fatty alcohol production in Y. lipolytica. Finally, we utilized this fatty alcohol reductase to generate a customized fatty alcohol, linolenyl alcohol, from α-linolenic acid. Overall, this work demonstrates Y. lipolytica is a robust chassis for diverse fatty alcohol production and highlights the capacity to obtain high titers and yields from a purely minimal media formulation directly from glucose without the need for complex additives.

Direct production of fatty alcohols from glucose using engineered strains of Yarrowia lipolytica

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.