Pyochelin Biosynthetic Metabolites Bind Iron and Promote Growth in Pseudomonads Demonstrating Siderophore-like Activity

Abstract

Pseudomonads employ several strategies to sequester iron vital for their survival including the use of siderophores such as pyoverdine and pyochelin. Similar in structure but significantly less studied are pyochelin biosynthetic byproducts, dihydroaeruginoic acid, aeruginoic acid, aeruginaldehyde (IQS), and aeruginol, along with two other structurally related molecules, aerugine and pyonitrins A−D, which have all been isolated from numerous Pseudomonad extracts. Because of the analogous substructure of these compounds to pyochelin, we hypothesized that they may play a role in iron homeostasis or have a biological effect on other bacterial species. Herein, we discuss the physiochemical evaluation of these molecules and disclose, for the first time, their ability to bind iron and promote growth in Pseudomonads.

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“…This feature was annotated as aeruginoic acid ( 3 ), which is a shunt product in the pyochelin biosynthesis pathway observed in Pseudomonas and Burkholderia spp. 70 , 71 . Aeruginoic acid is the oxidized form of aeruginaldehyde (also known as the integrated quorum sensing signal, or IQS), which has been proposed as a “fourth QS molecule” in P. aeruginosa , although this claim has been disputed 72 , 73 .…”

“…Aerugine has been previously isolated from Pseudomonas fluorescens and exhibits selective antifungal activity 76 . Recent work by Kaplan et al has indicated that aeruginaldehyde, aerugine, and aeruginoic acid have iron-binding activity with aeruginoic acid binding to Fe 3+ with a 1:1 ratio, aeruginaldehyde binding with a 2:1 ratio, and aerugine binding with a 3:1 ratio 71 . Unlike pyochelin, aeruginoic acid has a specific affinity for iron compared to other biologically relevant metals 71 .…”

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“…This feature was annotated as aeruginoic acid (3), which is a shunt product in the pyochelin biosynthesis pathway observed in Pseudomonas and Burkholderia spp. 70,71 . Aeruginoic acid is the oxidized form of aeruginaldehyde (also known as the integrated quorum sensing signal, or IQS), which has been proposed as a "fourth QS molecule" in P. aeruginosa, although this claim is disputed 72,73 .…”

“…Recent work by Kaplan et. al has indicated that aeruginaldehyde, aerugine, and aeruginoic acid all have iron-binding activity with aeruginoic acid binding to Fe 3+ with a 1:1 ratio, aeruginaldehyde binding with a 2:1 ratio, and aerugine binding with a 3:1 ratio 71 . Unlike pyochelin, aeruginoic acid has a speci c a nity for iron compared to other biologically relevant metals 71 .…”

“…al has indicated that aeruginaldehyde, aerugine, and aeruginoic acid all have iron-binding activity with aeruginoic acid binding to Fe 3+ with a 1:1 ratio, aeruginaldehyde binding with a 2:1 ratio, and aerugine binding with a 3:1 ratio 71 . Unlike pyochelin, aeruginoic acid has a speci c a nity for iron compared to other biologically relevant metals 71 . The largest abundance of thiazostatin is observed in the strain K56-2, which is likely why these intermediates are also detected in the strain K56-2.…”