Recently, the research team of Fengjiao Xin, an innovation team for food enzyme engineering, identified a specific type-A ferulic acid esterases from Gut Alistipes shahii of Bacteroide and determined the structure of this enzyme. The relevant research results were published as a cover story in the journal J. Agric. Food Chem (IF: 5.279) with the title “The α‑Helical Cap Domain of a Novel Esterase from Gut Alistipes shahii Shaping the Substrate-Binding Pocket”.

 

The human gut microbiota regulates food and nutritional metabolism, especially by encoding specific ferulic acid esterases (FAEs) to release functional ferulic acid (FA) from dietary fiber. Ferulic acid has rich health benefits, including antimicrobial activities and anti-inflammatory, anti-diabetes, and anti-cancer properties, as well as the prevention of cardiovascular disease. In this study, a 29 kDa FAE (AsFAE) from Alistipes shahii of Bacteroides was characterized and identified as the type-A FAE. The X-ray structure of AsFAE has been determined, revealing a unique α-helical domain comprising five α-helices, which was first characterized in FAEs from the gut microbiota. Further molecular docking analysis and biochemical studies revealed that Tyr100, Thr122, Tyr219, and Ile220 are essential for substrate binding and catalytic efficiency. Additionally, Glu129 and Lys130 in the cap domain shaped the substrate-binding pocket and affected the substrate preference. Collectively, our results provided biochemical and structural insights into the catalytic mechanism of FAEs from A. shahii, providing comprehensive information for understanding the dietary fiber metabolism in the gut and precision medicine and nutrition in view of the physiological importance of free FA through the gut−brain axis.

Our PhD student Xue Wei and Assistant researcher Yulu Wang as co-first authors, Researcher Fengzhong Wang and Fengjiao Xin as co-corresponding authors. This work was supported by the National Key Research and Development Plan “modern food processing and food storage and transportation technology and equipment” (2017YFD0400204), National Natural Science Foundation of China (31801475), and Central Public interest Scientific Institution Basal Research Fund (S2020JBKY-13).

 

 

Figure 1. Substrate-binding pocket of AsFAE. (A–C) Surface representation of AsFAE (A), TsEst (B), and BiFae1A (C) colored according to the electrostatic potentials (positive, blue; negative, red). (D) Structural comparison of the AsFAE with the TsEst (PDB entry: 4UHD, in light wheat). (E, F) Close-up views of substrate-binding pockets of AsFAE (E) and TsEst (F). The residues that may affect the substrate binding are shown as cyan and orange sticks, respectively.

Link to the paper: https://doi.org/10.1021/acs.jafc.1c00940