In-Silico Assessment of Erythritol Interactions with Microbial Enzymes Involved in Short-Chain Fatty Acid Metabolism

Abstract

Erythritol is a low-calorie polyol often used as a sugar substitute. While most of the ingested erythritol is absorbed in the small intestine and excreted unchanged [1-3], recent research has demonstrated that erythritol has different effects on microbial metabolites, such as short-chain fatty acids (SCFAs). The chemical basis of these observations remains unknown. In the present work, the expected interactions of erythritol with certain microbial enzymes involved in acetate metabolism, butyrate synthesis and carbohydrate utilization were studied. Molecular docking was carried out against acetate kinase (PDB: 4H0O), butyrate kinase (PDB: 1SAZ), phosphotransbutyrylase (PDB: 7VG9), and fructose-6-phosphate phosphoketolase (PDB: 3AHD) using SwissDock 2024 with the AutoDock Vina scoring tool. Erythritol was chosen as the docking ligand and the protein structures were retrieved from the Protein Data Bank. For each protein-ligand system, twenty poses were generated, and the best ranking pose was chosen based on the projected docking score. Fructose-6-phosphate phosphoketolase had the highest projected score with a docking score of −4.778 kcal/mol. The scores of acetate kinase, butyrate kinase and phosphotransbutyrylase were −4.175, −3.783 and −3.716 kcal/mol respectively . Under the used technique the relative ranking was fructose-6-phosphate phosphoketolase > acetate kinase > butyrate kinase > phosphotransbutyrylase. All the four selected microbial enzyme models were expected to be compatible with erythritol. Fructose-6-phosphate phosphoketolase received the highest docking score. These data furnish a first structural hypothesis on possible interactions between erythritol and enzymes. Nevertheless, binding affinity, enzymatic inhibition and physiological effects on the gut microbiota cannot be identified by docking scores alone [6–8]. Validation involves microbiological research and experimental enzyme testing.