Action and cooperation in alginate degradation by three enzymes from the human gut bacterium Bacteroides eggerthii DSM 20697

J Biol Chem. 2024 Sep;300(9):107596. doi: 10.1016/j.jbc.2024.107596. Epub 2024 Jul 19.

Abstract

Alginate is a polysaccharide consumed by humans in edible seaweed and different foods where it is applied as a texturizing hydrocolloid or in encapsulations of drugs and probiotics. While gut bacteria are found to utilize and ferment alginate to health-beneficial short-chain fatty acids, knowledge on the details of the molecular reactions is sparse. Alginates are composed of mannuronic acid (M) and its C-5 epimer guluronic acid (G). An alginate-related polysaccharide utilization locus (PUL) has been identified in the gut bacterium Bacteroides eggerthii DSM 20697. The PUL encodes two polysaccharide lyases (PLs) from the PL6 (BePL6) and PL17 (BePL17) families as well as a KdgF-like metalloprotein (BeKdgF) known to catalyze ring-opening of 4,5-unsaturated monouronates yielding 4-deoxy-l-erythro-5-hexoseulose uronate (DEH). B. eggerthii DSM 20697 does not grow on alginate, but readily proliferates with a lag phase of a few hours in the presence of an endo-acting alginate lyase A1-I from the marine bacterium Sphingomonas sp. A1. The B. eggerthii lyases are both exo-acting and while BePL6 is strictly G-block specific, BePL17 prefers M-blocks. BeKdgF retained 10-27% activity in the presence of 0.1-1 mM EDTA. X-ray crystallography was used to investigate the three-dimensional structure of BeKdgF, based on which a catalytic mechanism was proposed to involve Asp102, acting as acid/base having pKa of 5.9 as determined by NMR pH titration. BePL6 and BePL17 cooperate in alginate degradation with BeKdgF linearizing producing 4,5-unsaturated monouronates. Their efficiency of alginate degradation was much enhanced by the addition of the A1-I alginate lyase.

Keywords: KdgF-like enzyme; alginate; alginate lyase; carbohydrate processing; enzyme kinetics; enzyme mechanism; human gut microbiota; polysaccharide utilization locus; protein structure.

MeSH terms

  • Alginates* / chemistry
  • Alginates* / metabolism
  • Bacterial Proteins* / chemistry
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Bacteroides* / enzymology
  • Bacteroides* / metabolism
  • Gastrointestinal Microbiome
  • Hexuronic Acids
  • Humans
  • Polysaccharide-Lyases* / chemistry
  • Polysaccharide-Lyases* / metabolism

Substances

  • Alginates
  • Polysaccharide-Lyases
  • Bacterial Proteins
  • mannuronic acid
  • guluronic acid
  • poly(beta-D-mannuronate) lyase
  • Hexuronic Acids