Abstract
Aryl polyenes (APEs) are specialized polyunsaturated carboxylic acids that were identified in silico as the product of the most widespread family of bacterial biosynthetic gene clusters (BGCs). They are present in several Gram-negative host-associated bacteria, including multidrug-resistant human pathogens. Here, we characterize a biological function of APEs, focusing on the BGC from a uropathogenic Escherichia coli (UPEC) strain. We first perform a genetic deletion analysis to identify the essential genes required for APE biosynthesis. Next, we show that APEs function as fitness factors that increase protection from oxidative stress and contribute to biofilm formation. Together, our study highlights key steps in the APE biosynthesis pathway that can be explored as potential drug targets for complementary strategies to reduce fitness and prevent biofilm formation of multi-drug resistant pathogens.
Highlights
In a global search for novel types of bacterial secondary metabolites, we previously identified aryl polyenes (APEs) as the products of the most abundant biosynthetic gene cluster (BGC) family[1]
We previously identified APEs as the product of one of the most abundant bacterial BGC families and chose the BGC from E. coli CFT073 for in-depth characterization
While we and others propose that ApeF might be involved in malonyl chain extension (Fig. 3,11), the remaining pigmentation in the ΔapeF strain suggests this acyl carrier proteins (ACPs) is not absolutely essential for APEEccarboxylic acid biosynthesis and that perhaps the loss of this ACP could be partially complemented, for example by ApeE or by the ACP involved in E. coli fatty acid biosynthesis, AcpP30
Summary
In a global search for novel types of bacterial secondary metabolites, we previously identified aryl polyenes (APEs) as the products of the most abundant biosynthetic gene cluster (BGC) family[1]. APEs are present in most major bacterial genera throughout the Proteobacteria and Bacteroidetes They are often found in host-associated bacteria, including commensals as well as pathogens of humans, animals, and plants[1]. The main differences between APEs of different bacterial genera are in the polyene chain length and in the hydroxylation, methylation, or halogenation of the head group. This structural similarity is reflected in the observation that phylogenetically diverse APE BGCs share conserved core gene functions, resembling biosynthesis machinery for fatty acids and type II polyketides. Our current study addresses outstanding questions in APE biology, including the identity of the essential genes for in vivo biosynthesis and uncovering their biological function
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