Discovery of a fucoidan endo-4O-sulfatase: Regioselective 4O-desulfation of fucoidans and its effect on anticancer activity in vitro

Carbohydr Polym. 2021 Nov 1:271:118449. doi: 10.1016/j.carbpol.2021.118449. Epub 2021 Jul 16.

Abstract

Fucoidans are a class of sulfated fucose-containing bioactive polysaccharides produced by brown algae. The biological effects exhibited by fucoidans are thought to be related to their sulfation. However, the lack of methods for sulfation control does not allow for a reliable conclusion about the influence of the position of certain sulfate groups on the observed biological effects. We identified the gene encoding the endo-acting fucoidan sulfatase swf5 in the marine bacterium Wenyingzhuangia fucanilytica CZ1127T. This is the first report on the sequence of fucoidan endo-sulfatase. Sulfatase SWF5 belongs to the subfamily S1_22 of the family S1. SWF5 was shown to remove 4O-sulfation in fucoidans composed from the alternating α-(1→3)- and α-(1→4)-linked residues of sulfated L-fucose but not from fucoidans with the α-(1→3)-linked backbone. The endo-sulfatase was used to selectively prepare 4O-desulfated fucoidan derivatives. It was shown that the 4O-desulfated fucoidans inhibit colony formation of DLD-1 and MCF-7 cells less effectively than unmodified fucoidans. Presumably, 4O-sulfation makes a significant contribution to the anticancer activity of fucoidans.

Keywords: Anticancer activity; Fucoidan; Fucoidan endo-4O-sulfatase; Selective desulfation; Sulfatases subfamily S1_22.

MeSH terms

  • Amino Acid Sequence
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / isolation & purification
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Flavobacteriaceae / enzymology
  • Humans
  • Molecular Structure
  • Polysaccharides / chemical synthesis
  • Polysaccharides / pharmacology*
  • Substrate Specificity
  • Sulfatases / chemistry*
  • Sulfatases / isolation & purification

Substances

  • Antineoplastic Agents
  • Bacterial Proteins
  • Polysaccharides
  • fucoidan
  • Sulfatases

Supplementary concepts

  • Wenyingzhuangia fucanilytica