Synthesis and iron-binding properties of quinolobactin, a siderophore from a pyoverdine-deficient Pseudomonas fluorescens

Abstract

Quinolobactin is a new siderophore produced by a pyoverdine deficient mutant of Pseudomonas fluorescens. A simple and efficient synthesis of quinolobactin is described, starting from xanthurenic acid. The protonation constants of quinolobactin were determined by potentiometric titrations as pKa2 = 5.50+/-0.07, pKa1 = 10.30+/-0.05. The equilibria of the metal complexes were studied by means of spectrophotometric and potentiometric titrations. The overall stability constants of the quinolobactin-FeIII complexes was found to be log beta111 = 18.60+/-0.10, log beta121 = 32.60+/-0.20, log beta120 = 28.20+/-0.25 resulting in a pFeIII value of 18.2 at pH 7.4. The UV-visible spectral parameters of the [FeL2] are in agreement with a complex containing two ligands coordinated to one Fe3+ cation through the oxygen and nitrogen quinoline atoms.

The impact of metagenomic interplay on the mosquito redox homeostasis

“…XA is an iron chelator that binds to heme and iron, therefore reducing the amount of free heme for use in the Fenton reaction [32]. Interestingly, certain Pseudomonas bacteria produce quinolobactin, an efficient iron scavenger derived from XA in the tryptophan-kynurenine-xanthurenic acid pathway [33, 34]. This suggests there may be a contribution of bacteria-derived heme scavengers involved in maintaining midgut redox homeostasis.…”

Natural Products from Social Amoebae

“…In addition, Ppc‐1 ( 28 ) was synthesized to confirm its structure (Scheme c); xanthurenic acid ( 31 ) was reacted with neat thionyl chloride followed by addition of methanol to install the methoxy group, the resulting methyl ester was saponified with aqueous sodium hydroxide in methanol to give quinolobactin ( 32 ), a known siderophore . Prenylation of the latter with prenyl bromide under basic conditions gave Ppc‐1 ( 28 ).…”

“…The naturalproducts Pt-1-5 (23)(24)(25)(26)(27)were obtained from methanolic extractso ff ruiting bodies of P. tenuissimum;P pc-1 (28) was obtained analogously from fruiting bodies of P. pseudocandidum (Scheme 4). [22] To confirm the structure determined by NMR studies, Pt-4 (26)w as synthesized from 5-methoxyresorcinol (29)( Scheme 4b); installation of the acyl side chain was achieved by Friedel-Crafts acylation with butanoyl chloride.…”

“…In addition, Ppc-1 (28)w as synthesized to confirm its structure (Scheme 4c); [22] xanthurenic acid (31)w as reacted with neat thionyl chloride followedb ya ddition of methanol to install the methoxy group, the resulting methyl ester was saponified with aqueous sodium hydroxide in methanol to give quinolobactin (32), ak nown siderophore. [23] Prenylationo ft he latter with prenyl bromide under basic conditions gave Ppc-1 (28). Ppc-1 was shown to be am itochrondrial uncoupler [24] and derivatives of Ppc-1 weres hown to suppress production of interleukin-2, an immunoregulatory protein, in Jurkat cells.…”

Synthesis and biological evaluation of 1,4-naphthoquinones and quinoline-5,8-diones as antimalarial and schistosomicidal agents

“…These natural products are reported to exhibit a broad spectrum of biological activities including antibacterial, antifungal, antiviral, and antitumor properties. 5,6 Examples include streptonigrin, produced by an actinomycete ( Streptomyces flocculus ) 5a lavendamycin ( Streptomyces lavendulae ), 5h,6 and quinolobactin 7 ( Pseudomonas fluorescens ) (Figure 2). …”