With a better understanding of AI-2/luxS mediated gene regulation, we may be able to develop strategies for harnessing AI-2 quorum sensing for our advantage in bioreactor studies and ultimately in control of the bacterial pathogenicity.
showed that it is formed from acetateduring the normal course of cholesterol biosynthesis in rat liver homogenates (, J Biol Chem 1981, 256, 1067).
First description of the possibility of curing neuropsychiatric disorders with adiet enriched in linolenic acid (flaxseed oil) ().
Eberhard A et al.
In vitro biosynthesis of autoinducer 2 of ..
demonstrated a close association of the sulfogalactosyl diacylglycerol of rat brain with the process of myelination ().
First description of a high content in EPA (20:5n-3) in a prokaryote, the marine bacterium ().
the complete pathway for AI-2 synthesis.
He reported the first composition of the brain lipids including asaponifiable fraction (céphalote) soluble in ether and containing 5.8% ofphosphorus and a non-saponifiable fraction (cérébrote) containing 2.3% ofphosphorus ().
A method of quantifying autoinducer-2, ..
: 1950)">JImmunol 2005, 175, 3990).
Further analysis of bovine brain indicated the existence of another potentcapsaicin-like lipid, N-oleoyldopamine, which is similar toN-arachidonoyldopamine in its chemical structure and activity on vanilloidreceptors ().
Synthesis of theluxgene autoinducer ..
discovered and named "phytol" the alcohol whichesterifies the tetrapyrrole nucleus (), it wassynthesized in 1928.
Tswett M named "carotenoids" the group of various pigments he has separated fromplants ()
Synthesis of Autoinducer Analogs ..
several other lipopeptides containing various hydroxylated fatty acids have been isolated in tunicates.
A comprehensive survey of unique, unusual, and rare fatty acids incorporated into natural marine and terrestrial peptides obtained from fungi, fungal endophytes, lichenized ascomycetes, basidiomycetes, and actinomycetes may be found in an important review (Dembitsky VM, Int J Current Res Biosci Plant Biol 2017, 4, 7).
Pseudomonas aeruginosa mutant in synthesis of autoinducer molecules
In conclusion, although LuxS proteins have been extensively studied, no data were available with respect to their potential posttranslational regulation. We reported here, for the first time, the phosphorylation of the S. aureus AI-2 producer protein LuxS and identified Thr14 as the critical phosphoacceptor. This study suggests that environmental signals could trigger LuxS phosphorylation and presumably influence and/or regulate biological activities of the protein. Therefore, our findings may have important consequences for participating in and/or regulating the biological activities assigned to LuxS and Stk1, especially in quorum sensing and consequently in S. aureus virulence. Whether phosphorylation at position 14, which is highly conserved in the LuxS protein family, contributes to the regulation of these homologues is an attractive hypothesis that remains to be addressed.
doi:10.1021/jo00170a070 - ACS Publications Home Page
In order to assess the effect of LuxS phosphorylation on its activity, we took advantage of the fact that LuxS also plays a metabolic role in the activated-methyl cycle (AMC). AI-2 is the adduct of borate and a ribose derivative and is produced from S-adenosylhomocysteine (SAH) (). SAH is the by-product of numerous transmethylation reactions involving S-adenosylmethionine (SAM) (). Hydrolysis of SAH by the nucleosidase Pfs yields S-ribosyl--homocysteine (SRH) and adenine (Fig. ). SRH is then converted to homocysteine and 4,5-dihydroxy-2,3-pentanedione (DPD) by S-ribosylhomocysteinase (LuxS) (). DPD spontaneously cyclizes to form a furanone, which is complexed with borate to form AI-2. Each test to assess LuxS activity was prepared as described by Zhu et al. (). Briefly, SRH was prepared by incubating SAH with the nucleosidase Pfs for 1 h at room temperature, and the completion of the reaction was monitored spectrophotometrically using the difference in absorption between SAH and adenine. The reaction was initiated by the addition of LuxS and monitored continuously at 412 nm in a spectrophotometer at room temperature. Surprisingly, neither of the LuxS mutants (T14A and T14D), was able to show any enzymatic activity, while the LuxS_WT strain generated the expected activity profile (data not shown). These results indicate that the Thr14 residue is critical for LuxS activity, as the Ala replacement was not able to restore LuxS activity as expected. In order to bypass this problem, we decided to compare the activity of the LuxS protein purified from the pETPhos_LuxS strain, which corresponds to the nonphosphorylated isoform of LuxS, with that of p-LuxS, which corresponds to the LuxS phosphorylated isoform purified from the pETDuet system. The phosphorylation state of the p-LuxS protein was confirmed by mass spectrometry prior to the assay and indicated that 95% of the protein was phosphorylated on the Thr14 residue. As shown in Fig. , activity of phosphorylated LuxS (p-LuxS) was almost totally abrogated compared to the activity of nonphosphorylated LuxS, indicating that the Stk1-mediated phosphorylation of LuxS seems to represent a key mechanism for regulating and/or controlling its activity. Phosphorylation seems to modulate LuxS activity with a rather strict on/off mechanism. However, further work is needed to understand at a molecular level whether and how phosphorylation of LuxS modifies the overall structure of this protein.