Strong inhibitory activities and action modes of lipopeptides on lipase

J Enzyme Inhib Med Chem. 2020 Dec;35(1):897-905. doi: 10.1080/14756366.2020.1734798.

Abstract

Lipopeptides have been reported to exhibit anti-obesity effects. In this study, we obtained a Bacillus velezensis strain FJAT-52631 that could coproduce iturins, fengycins, and surfactins. Results showed that the FJAT-52631 crude lipopeptide, purified fengycin, iturin, and surfactin standards exhibited strong inhibition activities against lipase with dose-dependence manners (half maximal inhibitory concentration (IC50) = 0.011, 0.005, 0.056, and 0.005 mg/mL, respectively). Moreover, fengycin and surfactin had the comparable activities with orlistat, but iturin not. It was revealed that the inhibition mechanism and type of the lipopeptides were reversible and competitive. The quenching mechanism of lipase was static and only one binding site between lipase and lipopoeptide was inferred from the fluorescence analysis. The docking analysis displayed that fengycin and surfactin could directly interact with the active amino acid residues (Ser or Asp) of lipase, but not with iturin. Our work suggests that the B. velezensis lipopeptides would have great potential to act as lipase inhibitors.

Keywords: Lipopeptides; action mode; inhibitory activities; lipase.

MeSH terms

  • Bacillus / chemistry
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Lipase / antagonists & inhibitors*
  • Lipase / metabolism
  • Lipopeptides / chemistry
  • Lipopeptides / isolation & purification
  • Lipopeptides / pharmacology*
  • Molecular Docking Simulation
  • Molecular Structure
  • Mucor / enzymology
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Lipopeptides
  • Lipase

Supplementary concepts

  • Bacillus velezensis

Grants and funding

This work was supported by the Young Elite Scientists Sponsorship Programme by CAST under Grant [2017QNRC001]; the Fujian Special Fund for Scientific Research Institutes in the Public Interest under Grant [2019R1034-6 and 2019R1034-5]; and the Science and Technology Innovation Team Programme of Fujian Academy of Agricultural Sciences under Grant [STIT2017-1–11].