A Family of Nonribosomal Peptides Modulate Collective Behavior in Pseudovibrio Bacteria Isolated from Marine Sponges**

Abstract

Although swarming motility and biofilms are opposed collective behaviors, both contribute to bacterial survival and host colonization. Pseudovibrio bacteria have attracted attention because they are part of the microbiome of healthy marine sponges. Two‐thirds of Pseudovibrio genomes contain a member of a nonribosomal peptide synthetase‐polyketide synthase gene cluster family, which is also found sporadically in Pseudomonas pathogens of insects and plants. After developing reverse genetics for Pseudovibrio, we isolated heptapeptides with an ureido linkage and related nonadepsipeptides we termed pseudovibriamides A and B, respectively. A combination of genetics and imaging mass spectrometry experiments showed heptapetides were excreted, promoting motility and reducing biofilm formation. In contrast to lipopeptides widely known to affect motility/biofilms, pseudovibriamides are not surfactants. Our results expand current knowledge on metabolites mediating bacterial collective behavior.

PEARL-catalyzed peptide bond formation after chain reversal during the biosynthesis of non-ribosomal peptides

“…We compiled the UreaC domains in the MiBiG database based on collinearity to product structures (e.g. anabaenopeptins, 37 bulbfieramide, 38 chitinimide, 39 and pseudovibriomide 40 ) as well as examples with in vitro confirmation of the ureido formation enzyme activity (e.g. syringolin A, 27 pacidamycin, 41 antipain, 42 and muraymycin 42 ).…”

“…For ureido-forming BGCs that contain two A domains, the specificity of the A domain of the loading A-T didomain usually corresponds to the amino acid at the terminal position of the ureido group. 37,38,40,42 Similarly, the A domain specificity of the first extension module (UreaC-A-T) usually corresponds to the internal amino acid of the ureido group. 37,38,40,42 After ureido bond formation, the amino acid at the internal position is still attached to the PCP as a thioester and can be further extended by NRPS/PKS biochemistry.…”

“…37,38,40,42 Similarly, the A domain specificity of the first extension module (UreaC-A-T) usually corresponds to the internal amino acid of the ureido group. 37,38,40,42 After ureido bond formation, the amino acid at the internal position is still attached to the PCP as a thioester and can be further extended by NRPS/PKS biochemistry. 42 However, the terminal amino acid is left with an unactivated carboxylate and can no longer be extended by the assembly line chemistry.…”