title: Antimicrobial peptide gramicidin S is accumulated in granules of producer cells for storage of bacterial phosphagens.
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.
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Organic Chemistry, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Berditsch
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Organic Chemistry, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Trapp
authors.affiliation: KIT, Institute of Biological Interfaces (IBG-2), P.O.B. 3640, 76021 Karlsruhe, Germany.
authors.forename: Sergii
authors.initials: S
authors.lastname: Afonin
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Organic Chemistry, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Organic Chemistry, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Misiewicz
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Organic Chemistry, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany.
authors.forename: Joana
authors.initials: J
authors.lastname: Turkson
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Organic Chemistry, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany.|KIT, Institute of Biological Interfaces (IBG-2), P.O.B. 3640, 76021 Karlsruhe, Germany.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000591:Amino Acid Isomerases / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D056449:Bacillales / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D003594:Cytoplasmic Granules / Q000378:metabolism* / Q000648:ultrastructure; D015964:Gene Expression Regulation, Bacterial; D006096:Gramicidin / Q000096:biosynthesis*; D006160:Guanosine Triphosphate / Q000096:biosynthesis; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D009876:Operon; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D007527:Isoenzymes; D009097:Multienzyme Complexes; D006096:Gramicidin; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D013869:Thiolester Hydrolases; D000591:Amino Acid Isomerases; D010453:Peptide Synthases; C020831:gramicidin-S-synthetase 2