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

Area of Science:

• Microbiology
• Biochemistry
• Cancer Biology

Background:

• Colorectal cancer progression is linked to Fusobacterium nucleatum and reduced spermidine acetylation.
• Dietary tannins are also implicated in colorectal cancer pathogenesis.

Purpose of the Study:

• To investigate the structural and functional differences of a novel F. nucleatum tannase (TanBFnn) compared to its Lactobacillus plantarum counterpart.
• To elucidate the inhibitory mechanisms of polyamines, specifically acetylated spermidine derivatives, on TanBFnn activity.
• To understand how TanBFnn activity and metabolic inhibitors affect F. nucleatum survival.

Main Methods:

• X-ray crystallography and molecular dynamics simulations were employed to analyze TanBFnn structure and substrate interactions.
• Biochemical assays were performed to assess the hydrolytic activity of TanBFnn.
• Studies examined the impact of spermidine derivatives and gallotannins on F. nucleatum growth and toxicity.

Main Results:

• F. nucleatum tannase (TanBFnn) exhibits significant structural differences from L. plantarum tannase, particularly in its active site flap and substrate accessibility.
• Polyamines, including N8-acetylated spermidine, bind to a cavity near the active site and inhibit TanBFnn activity.
• Spermidine derivatives potentiate the toxicity of gallotannins to F. nucleatum.

Conclusions:

• The activity of TanBFnn is modulated by polyamine binding, affecting its ability to process dietary tannins.
• The interplay between TanBFnn's detoxicant function and the presence of spermidine derivatives influences F. nucleatum's viability.
• These findings offer insights into the metabolic strategies of F. nucleatum in the context of colorectal cancer.