Biosynthesis of Pseudomonas‐Derived Butenolides

Abstract

Butenolides are well‐known signaling molecules in Gram‐positive bacteria. Here, we describe a novel class of butenolides isolated from a Gram‐negative Pseudomonas strain, the styrolides. Structure elucidation was aided by the total synthesis of styrolide A. Transposon mutagenesis enabled us to identify the styrolide biosynthetic gene cluster, and by using a homology search, we discovered the related and previously unknown acaterin biosynthetic gene cluster in another Pseudomonas species. Mutagenesis, heterologous expression, and identification of key shunt and intermediate products were crucial to propose a biosynthetic pathway for both Pseudomonas‐derived butenolides. Comparative transcriptomics suggests a link between styrolide formation and the regulatory networks of the bacterium.

Deciphering Chemical Mediators Regulating Specialized Metabolism in a Symbiotic Cyanobacterium

“…[22,23] Butenolides are well-known signaling molecules in Gram-positive bacteria but recently also gained attention as potential signaling compounds in Pseudomonas. [23] They are structurally related to tetronates and γ-butyrolactones. Many linear tetronates are inhibitors of phosphatase enzymes and interfere with signaling pathways that depend on phosphorylation, [13] whereas γ-butyrolactones, like the A-factor, are prototype QS signals.…”

“…The observed signaling activity of the nostoclides and nostovalerolactone is nevertheless in line with the structural features that these compounds share with many other bacterial QS mediators. The nostoclides belong to the class of butenolides, which share a 2‐furanone moiety [22, 23] . Butenolides are well‐known signaling molecules in Gram‐positive bacteria but recently also gained attention as potential signaling compounds in Pseudomonas [23] .…”

Beyond Soil-Dwelling Actinobacteria: Fantastic Antibiotics and Where to Find Them

“…It is in this area, the less easily identified BGCs, where Pseudomonas exhibit big potential for novel chemistry discovery. In fact, the use of untargeted methods such as the generation of transposon mutant libraries of bioactive Pseu-domonas strains has led to the discovery of secondary metabolites such as the butanolide molecules styrolides A (Figure 15) and B [380], or the antimicrobial 7-hydroxytropolone (Figure 15) in two different biocontrol Pseudomonas strains [340,341], presenting this as a promising strategy to uncover useful secondary metabolites. Finally, and perhaps surprisingly, not many RiPPs have been characterized in Pseudomonas strains, with the notable exceptions of the redox cofactor pyrroloquinoline quinone (PQQ) (Figure 15) [39] and the recently discovered and highly unusual 3-thiaglutamate (Figure 15) [381].…”

“…It is in this area, the less easily identified BGCs, where Pseudomonas exhibit big potential for novel chemistry discovery. In fact, the use of untargeted methods such as the generation of transposon mutant libraries of bioactive Pseudomonas strains has led to the discovery of secondary metabolites such as the butanolide molecules styrolides A ( Figure 15 ) and B [ 380 ], or the antimicrobial 7-hydroxytropolone ( Figure 15 ) in two different biocontrol Pseudomonas strains [ 340 , 341 ], presenting this as a promising strategy to uncover useful secondary metabolites.…”

Effect of Selected Silyl Groups on the Anticancer Activity of 3,4-Dibromo-5-Hydroxy-Furan-2(5H)-One Derivatives

“…Furan-2(5H)-one scaffold and its variations are widely present in many bioactive natural products [4,5]. The modification of this structural motif led previously to multiple derivatives with a wide range of activity against cancers [6][7][8][9], bacterial infections [10,11], and fungus [12,13].…”