Antimicrobial peptide gramicidin S is accumulated in granules of producer cells for storage of bacterial phosphagens

Sci Rep. 2017 Mar 15:7:44324. doi: 10.1038/srep44324.

Abstract

Many antimicrobial peptides are synthesized non-ribosomally in bacteria, but little is known about their subcellular route of biosynthesis, their mode of intracellular accumulation, or their role in the physiology of the producer cells. Here, we present a comprehensive view on the biosynthesis of gramicidin S (GS) in Aneurinibacillus migulanus, having observed a peripheral membrane localization of its synthetases. The peptide gets accumulated in nano-globules, which mature by fusion into larger granules and end up within vacuolar structures. These granules serve as energy storage devices, as they contain GS molecules that are non-covalently attached to alkyl phosphates and protect them from dephosphorylation and premature release of energy. This finding of a fundamentally new type of high-energy phosphate storage mechanism can explain the curious role of GS biosynthesis in the physiology of the bacterial producer cells. The unknown role of the GrsT protein, which is part of the non-ribosomal GS synthetase operon, can thus be assumed to be responsible for the biosynthesis of alkyl phosphates. GS binding to alkyl phosphates may suggest its general affinity to phosphagens such as ATP and GTP, which can represent the important intracellular targets in pathogenic bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Amino Acid Isomerases / genetics
  • Amino Acid Isomerases / metabolism
  • Anti-Bacterial Agents / biosynthesis*
  • Bacillales / genetics
  • Bacillales / metabolism*
  • Bacillales / ultrastructure
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Cell Membrane / metabolism
  • Cell Membrane / ultrastructure
  • Cytoplasmic Granules / metabolism*
  • Cytoplasmic Granules / ultrastructure
  • Gene Expression Regulation, Bacterial*
  • Gramicidin / biosynthesis*
  • Guanosine Triphosphate / biosynthesis
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism
  • Operon
  • Peptide Synthases / genetics
  • Peptide Synthases / metabolism
  • Protein Binding
  • Thiolester Hydrolases / genetics
  • Thiolester Hydrolases / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Isoenzymes
  • Multienzyme Complexes
  • Gramicidin
  • Guanosine Triphosphate
  • Adenosine Triphosphate
  • Thiolester Hydrolases
  • Amino Acid Isomerases
  • Peptide Synthases
  • gramicidin-S-synthetase 2