From wheat bran to 4-vinylguaiacol: A green bioprocess featuring in situ product recovery.

Valorizing agro-industrial byproducts such as wheat bran (WB) through microbial and enzymatic processing offers a sustainable route to high-value aromatic compounds like 4-vinylguaiacol (4VG). This study reports a novel one-pot biocatalytic system that couples the enzymatic hydrolysis of WB (UltrafloXL) - releasing ferulic acid (FA) and sugars - with the microbial conversion of FA into 4VG by an engineered E. coli strain expressing ferulic acid decarboxylase (Fdc) under a phenol-inducible promoter. The process is self-sustaining: FA acts both as the enzymatic substrate and as the inducer for Fdc expression, while glucose released from WB sustains microbial growth. Integrated in situ product recovery (ISPR) using a tea-bag resin system enhances yields while streamlining purification. The system achieved a 4VG yield of approximately 2.0 mg/g of WB, corresponding to an overall conversion efficiency of ∼88 %. Proof-of-concept experiments at 0.5 L scale showed efficient extraction (96 ± 1.5 %) and purification (76 ± 1.2 %) yields, together with a low materials-based cost, supporting the techno-economic viability of 4VG production from renewable feedstocks. To our knowledge, this is the first report of a WB-based 4VG biosynthesis using an engineered E. coli in a system where FA acts both as substrate and activator. This integrated, autoinductive platform represents a green alternative for aromatic compounds production in alignment with bioeconomy principles.