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The Gram-negative bacteria  Photorhabdus  and  Xenorhabdus  are known to produce a variety of different natural products (NP). These compounds play different roles since the bacteria live in symbiosis with nematodes and are pathogenic to insect larvae in the soil. Thus, a fine tuned regulatory system controlling NP biosynthesis is indispensable. Global regulators such as Hfq, Lrp, LeuO and HexA have been shown to influence NP production of  Photorhabdus  and  Xenorhabdus . Additionally, photopyrones as quorum sensing (QS) signals were demonstrated to be involved in the regulation of NP production in  Photorhabdus.  In this study, we investigated the role of another possible QS signal, autoinducer-2 (AI-2), in regulation of NP production. The AI-2 synthase (LuxS) is widely distributed within the bacterial kingdom and has a dual role as a part of the activated methyl cycle pathway, as well as being responsible for AI-2 precursor production. We deleted  luxS  in three different entomopathogenic bacteria and compared NP levels in the mutant strains to the wild type (WT) but observed no difference to the WT strains. Furthermore, the absence of the small regulatory RNA  micA , which is encoded directly upstream of  luxS , did not influence NP levels. Phenotypic differences between the  P. luminescens luxS  deletion mutant and an earlier described  luxS  deficient strain of  P. luminescens  suggested that two phenotypically different strains have evolved in different laboratories.

LuxS-dependent AI-2 production is not involved in global regulation of natural product biosynthesis inPhotorhabdusandXenorhabdus