Solonamides, a Group of Cyclodepsipeptides, Influence Motility in the Native Producer Photobacterium galatheae S2753

The marine bacterium Photobacterium galatheae S2753 produces a group of cyclodepsipeptides, called solonamides, which impede the virulence but not the survival of Staphylococcus aureus. In addition to their invaluable antivirulence activity, little is known about the biosynthesis and physiological function of solonamides in the native producer. This study generated a solonamide-deficient (Δ ) mutant by in-frame deletion of the gene, thereby identifying the core gene for solonamide biosynthesis. By annotation from antiSMASH, the biosynthetic pathway of solonamides in S2753 was also proposed. Mass spectrometry analysis of cell extracts found that deficiency of solonamide production influenced the production of a group of unknown compounds but otherwise did not alter the overall secondary metabolite profile. Physiological comparison between Δ and wild-type S2753 demonstrated that growth dynamics and biofilm formation of both strains were similar; however, the Δ mutant displayed reduced motility rings compared to the wild type. Reintroduction of restored solonamide production and motility to the mutant, indicating that solonamides influence the motility behavior of S2753. Proteomic analysis of the Δ and wild-type strains found that eliminating solonamides influenced many cellular processes, including swimming-related proteins and proteins adjusting the cellular cyclic di-GMP concentration. In conclusion, our results revealed the biosynthetic pathway of solonamides and their ecological benefits to S2753 by enhancing motility, likely by altering the motile physiology. The broad range of bioactive potentials of cyclodepsipeptides makes these compounds invaluable in the pharmaceutical industry. Recently, a few novel cyclodepsipeptides have been discovered in marine ; however, their biosynthetic pathways remain to be revealed. Here, we demonstrated the biosynthetic genetic basis and pathway of the antivirulence compounds known as solonamides in S2753. This can pave the way for the biological overproduction of solonamides on an industrial scale. Moreover, the comparison of a solonamide-deficient mutant and wild-type S2753 demonstrated that solonamides stimulate the swimming behavior of S2753 and also influence a few key physiological processes of the native producers. These results evidenced that, in addition to their importance as novel drug candidates, these compounds play a pivotal role in the physiology of the producing microorganisms and potentially provide the