Efficient transformation of lignin-derived syringaldehyde to syringyl acetate via tandem catalysis with alcohol dehydrogenase and lipase

Recombinant E. coli ADH6–GDH carrying ADH6 and GDH was constructed for bioreduction. • ADH6–GDH whole-cell fully converted 40 mM syringaldehyde to syringyl alcohol. • Substrate spectrum was explored using lignin-derived aldehydes via bioreduction. • Lipase Novozym 435 enabled the conversion of syringyl alcohol to syringyl acetate. • Tandem biocatalysis with reductase and lipase was used to synthesize aromatic esters. Efficient valorization of lignin-derived aromatics remains a key challenge in sustainable chemistry. Biobased aromatic alcohols and esters are important value-added compounds widely used in fragrances, pharmaceutical intermediates, fine chemicals, and functional materials. In this study, a whole-cell biocatalytic system co-expressing alcohol dehydrogenase (ADH6) from Saccharomyces cerevisiae and glucose dehydrogenase (GDH) was developed for the efficient conversion of syringaldehyde to syringyl alcohol. The GDH-based cofactor regeneration module enabled in situ reduced nicotinamide adenine dinucleotide phosphate (NADPH) supply, thereby improving catalytic efficiency while reducing the dependence on external cofactors. Under optimized conditions, the system achieved a high analytical yield of 98.3% at 40 mM syringaldehyde in an aqueous system, representing, to the best of our knowledge, the highest substrate concentration reported so far for this biocatalytic conversion. The substrate spectrum was further evaluated using representative lignin-derived aromatic aldehydes, including cinnamaldehyde, p -anisaldehyde, vanillin, and 3,4-dimethoxybenzaldehyde. These substrates were converted into cinnamyl alcohol, 4-methoxybenzyl alcohol, vanillyl alcohol, and 3,4-dimethoxybenzyl alcohol, respectively. Cinnamaldehyde, p -anisaldehyde, and 3,4-dimethoxybenzaldehyde afforded the corresponding alcohols with analytical yields of 99%, whereas vanillin gave vanillyl alcohol with an analytical yield of 86% after 4 h. Molecular docking indicated that these substrates could bind within the ADH6 active pocket through similar orientations, supported by hydrogen-bonding and hydrophobic interactions, providing structural explanation for the observed substrate adaptability. In addition, coupling with immobilized lipase Novozym 435 enabled the conversion of syringyl alcohol into syringyl acetate via transesterification. This work established an efficient tandem biocatalysis with reductase and lipase for upgrading of lignin-derived aromatic compounds. Download: Download high-res image (100KB) Download: Download full-size image