The Chemical Structure of Widespread Microbial Aryl Polyene Lipids

Abstract

Biosynthetic gene clusters (BGC) involved in aryl polyene (APE) biosynthesis are supposed to represent the most widespread BGC in the bacterial world.[1–3] Still, only hydrolysis products[4–8] and not the full-length product(s) have been identified, hindering studies on their biosynthesis and natural function. Here, we apply subsequent chromatographic separations to purify the aryl polyene-containing lipids (APELs) from the entomopathogenic bacterium Xenorhabdus doucetiae. Structure elucidation using a combination of isotope labeling, nuclear magnetic resonance techniques, and tandem mass spectrometry reveals an array of APELs featuring an all-trans C26:5 conjugated fatty acyl and a galactosamine-phosphate-glycerol moiety. In combination with extensive genetic studies, this research broadens the bacterial natural product repertoire and paves the way for future functional characterization of this almost universal microbial compound class. Due to their protective function against reactive oxygen species,[5,9] APELs might be important for virulence or symbiosis, mediating organismic interactions in several ecological niches.

Genome analysis suggests the bacterial family Acetobacteraceae is a source of undiscovered specialized metabolites

“…Aryl polyenes (APEs) are bacterial pigments produced abundantly by the phylum Proteobacteria, and like carotenoids these unsaturated molecules play a role in the capture of free radicals to prevent oxidative stress (Scho ¨ner et al 2016). The biosynthesis of APEs involves the loading of an aromatic precursor (usually 4-hydroxybenzoic acid) onto an acyl carrier protein (ACP), named ApeE, in a process catalyzed by ApeH (Grammbitter et al 2020). The central enzyme b-ketoacyl-ACP synthase (ApeO/ApeC) elongates the chain in a decarboxylation Claisen condensation with malonate units, and the cetone product is reduced to alcohol by ApeQ and dehydrated to a double bond by ApI/ApeP in an iterative process.…”

Global analysis of biosynthetic gene clusters reveals conserved and unique natural products in entomopathogenic nematode-symbiotic bacteria

“…1d ) are found exclusively in 76% of Xenorhabdus strains. The ape BGC synthesizing arylpolyene lipids 34 ( Supplementary Fig. 2 ) that protect the bacteria from oxidative stress and promote biofilm formation 35 is the most prominent GCF among Gram-negative bacteria 25,34 .…”

“…BGC expressions need to be in an insect mimicking medium 39,70 or under iron-limited conditions 60 ); 2) compounds that are membrane-bound (e.g. arylpolyene lipids 34 ) and that are difficult to be detected by standard LC/MS methods (e.g. compounds that are extremely hydrophilic/hydrophobic, too small/large, or poorly ionized/fragmented).…”

Genome Analysis Suggests The Bacterial Family Acetobacteraceae is a Source of Undiscovered Specialized Metabolites

“…Aryl polyenes (APEs) are bacterial pigments produced abundantly by the phylum Proteobacteria, and like carotenoids these unsaturated molecules play a role in the capture of free radicals to prevent oxidative stress (Schöner et al 2016). The biosynthesis of APEs involves the loading of an aromatic precursor (usually 4-hydroxybenzoic acid) onto an acyl carrier protein (ACP), named ApeE, in a process catalyzed by ApeH (Grammbitter et al 2020). The central enzyme β-ketoacyl-ACP synthase (ApeO/ApeC) elongates the chain in a decarboxylation Claisen condensation with malonate units, and the cetone product is reduced to alcohol by ApeQ and dehydrated to a double bond by ApI/ApeP in an iterative process.…”