LAUSR

Natural phenethyl acetate (PEA), phenylacetic acid (PAA), ethyl phenylacetate (Et-PA), and phenethyl phenylacetate (PE-PA) are highly wanted aroma chemicals, but with limited availability and high price. Here we developed green, sustainable, and efficient bioproduction of these chemicals as natural products from renewable feedstocks. PEA and PAA were synthesized from L -phenylalanine ( L -Phe) via novel six-enzyme and five-enzyme cascade, respectively. Whole-cell based cascade biotransformation of 100 mM L -Phe in a two-phase system (aqueous-organic ratio: 1/0.5, v/v) containing ethyl oleate or biodiesel as green solvent gave 13.6 g/L PEA (83.1% conv.) and 11.6 g/L PAA (87.1% conv.), respectively. Coupled fermentation and biotransformation approach produced 10.4 g/L PEA and 9.2 g/L PAA from glucose or glycerol, respectively. The biosynthesized PAA was converted to natural Et-PA and PE-PA by esterification using lipases with ethanol or 2-phenylethanol derived from sugar, affording 2.7 g/L Et-PA (83.1% conv.) and 4.6 g/L PE-PA (96.3% conv.), respectively.