This article proposes a biosynthetic route for synthesizing filbertone, the principal flavor compound of hazelnut, through a multienzyme cascade. The pathway uses D-amino acid oxidase, threonine deaminase, and a regioselective transketolase from Geobacillus stearothermophilus to produce a sustainable, natural hazelnut aroma precursor, addressing industrial demands for regulated natural compounds.

Biocatalysis gains significant industrial interest due to its controlled stereoselectivity and use of mild process conditions. Here, a biosynthetic route is proposed for the synthesis of filbertone (5-methyl-2-hepten-4-one, 1), which is the principal flavor compound of hazelnut. The enantiomeric purity of the industrially synthesized compound is defined, contrary to the natural aroma, which varies according to the source of the nut, extraction conditions, and treatments. The novel synthetic pathway for a hazelnut aroma precursor proposed here consists of a multienzyme cascade, which starts from the two amino acids D-Ile and L-Thr that are individually converted by enzyme catalysts, i.e., D-amino acid oxidase and threonine deaminase, followed by CC ligation of the obtained products, allowing a potentially sustainable production of the natural aroma. The most critical step is CC ligation, which uses two carbonyl compounds as starting material. This step is catalyzed by a regioselective transketolase (TK) that originates from Geobacillus stearothermophilus. The approach holds promise for the industrial production of natural hazelnut aroma precursors, addressing the growing demand in the aroma industry for synthesis methods that sustain the regulatory claims for natural compounds.