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Biotechnol Bioeng. 2014 Jan;111(1):115-24. doi: 10.1002/bit.24993. Epub 2013 Jul 22.

Metabolic engineering of Saccharomyces cerevisiae for the production of 2-phenylethanol via Ehrlich pathway.

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School of Chemical and Biological Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-744, Korea.


2-Phenylethanol (2-PE), a fragrance compound with a rose-like odor, is widely used in perfumery and cosmetics. Here, we report the first metabolic engineering approach for 2-PE production in Saccharomyces cerevisiae. 2-PE can be produced from the catabolism of L-phenylalanine via Ehrlich pathway, consisting of transamination to phenylpyruvate by Aro9, decarboxylation to phenylacetaldehyde by Aro10, and reduction to 2-PE by alcohol dehydrogenases. We demonstrated that Ald3 is mainly responsible for phenylacetaldehyde oxidation, competing with 2-PE production. ALD3 deletion strain overexpressing ARO9 and ARO10 both by episomal overexpression and by induction of the endogenous genes through overexpression of Aro80 transcription factor, produced 4.8 g/L 2-PE in a medium containing 10 g/L L-phenylalanine as a sole nitrogen source. Considering the cytotoxicity of 2-PE, this production titer is almost the upper limit that can be reached in batch cultures, suggesting the great potential of this yeast strain for 2-PE production. 2-PE production was further increased by applying two-phase fermentation method with polypropylene glycol 1200 as an extractant, reaching 6.1 g/L 2-PE in organic phase with the molar yield of 82.5%, which is about ninefold increase compared with wild type.


2-phenylethanol; Ald3; Aro10; Aro80; Aro9; Ehrlich pathway; Saccharomyces cerevisiae

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