Characterization of two siderophores produced by Bacillus megaterium: A preliminary investigation into their potential as therapeutic agents.
Bacillus megaterium
Iron overload
Schizokinen
Siderophores
Journal
Biochimica et biophysica acta. General subjects
ISSN: 1872-8006
Titre abrégé: Biochim Biophys Acta Gen Subj
Pays: Netherlands
ID NLM: 101731726
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
30
04
2020
revised:
06
06
2020
accepted:
12
06
2020
pubmed:
23
6
2020
medline:
15
12
2020
entrez:
23
6
2020
Statut:
ppublish
Résumé
Microorganisms produce siderophores in order to scavenge iron from the environment and this study focuses on the characterization of the two siderophores secreted by Bacillus megaterium. The general biological properties and pharmacokinetics following oral application of these compounds are reported. Under optimized culture conditions, the siderophores were harvested, purified by chromatography and identified using LC-MS and NMR. Two dihydroxamate siderophores were isolated, schizokinen (MW = 420) and schizokinen imide (MW = 402). Both compounds demonstrate strong antioxidant activity and were found to be relatively nontoxic to both human hepatocellular carcinoma (Huh7) and peripheral blood mononuclear cells. The siderophores possess a strong affinity for iron(III) and decrease the levels of the labile iron pool (LIP) in iron-loaded cells in a concentration-dependent manner. Schizokinen, was detected as both the free siderophore and the iron complex in the plasma and urine of rats after oral gavage. However, the bioavailability was low and thus schizokinen, like deferoxamine, has no potential as an orally active iron chelator for the treatment of systemic iron overload. By virtue of the high affinity of schizokinen for tribasic metals, this siderophore does have considerable potential for the chelation of gallium(III) and the development of clinical diagnostic reagents.
Sections du résumé
BACKGROUND
Microorganisms produce siderophores in order to scavenge iron from the environment and this study focuses on the characterization of the two siderophores secreted by Bacillus megaterium. The general biological properties and pharmacokinetics following oral application of these compounds are reported.
METHODS
Under optimized culture conditions, the siderophores were harvested, purified by chromatography and identified using LC-MS and NMR. Two dihydroxamate siderophores were isolated, schizokinen (MW = 420) and schizokinen imide (MW = 402).
RESULTS
Both compounds demonstrate strong antioxidant activity and were found to be relatively nontoxic to both human hepatocellular carcinoma (Huh7) and peripheral blood mononuclear cells. The siderophores possess a strong affinity for iron(III) and decrease the levels of the labile iron pool (LIP) in iron-loaded cells in a concentration-dependent manner. Schizokinen, was detected as both the free siderophore and the iron complex in the plasma and urine of rats after oral gavage.
CONCLUSIONS
However, the bioavailability was low and thus schizokinen, like deferoxamine, has no potential as an orally active iron chelator for the treatment of systemic iron overload.
GENERAL SIGNIFICANCE
By virtue of the high affinity of schizokinen for tribasic metals, this siderophore does have considerable potential for the chelation of gallium(III) and the development of clinical diagnostic reagents.
Identifiants
pubmed: 32565293
pii: S0304-4165(20)30182-3
doi: 10.1016/j.bbagen.2020.129670
pii:
doi:
Substances chimiques
Antioxidants
0
Hydroxamic Acids
0
Iron Chelating Agents
0
Siderophores
0
schizokinen
35418-52-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
129670Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.