A structurally unique Fusobacterium nucleatum tannase provides detoxicant activity against gallotannins and pathogen resistance

A new tannase enzyme from the cancer‐related pathogen Fusobacterium nucleatum is important for the survival of the bacteria under the stress conditions derived from the presence of dietary gallotannins. Using structural studies and molecular modelling we describe new structural features for this enzyme. The inhibition of the enzyme by spermidine and its acetylated derivatives conduce to higher susceptibility to diet phenolic gallotannins and decreased fitness of F. nucleatum. Summary Colorectal cancer pathogenesis and progression is associated with the presence of Fusobacterium nucleatum and the reduction of acetylated derivatives of spermidine, as well as dietary components such as tannin‐rich foods. We show that a new tannase orthologue of F. nucleatum (TanBFnn) has significant structural differences with its Lactobacillus plantarum counterpart affecting the flap covering the active site and the accessibility of substrates. Crystallographic and molecular dynamics analysis revealed binding of polyamines to a small cavity that connects the active site with the bulk solvent which interact with catalytically indispensable residues. As a result, spermidine and its derivatives, particularly N8‐acetylated spermidine, inhibit the hydrolytic activity of TanBFnn and increase the toxicity of gallotannins to F. nucleatum. Our results support a model in which the balance between the detoxicant activity of TanBFnn and the presence of metabolic inhibitors can dictate either conducive or unfavourable conditions for the survival of F. nucleatum.