L-Homoserine lactone

A. Chatterjee, Y. Cui, Y. Liu, C. K. Dumenyo, A. K. Chatterjee, Inactivation of rsmA leads to overproduction of extracellular pectinases, cellula.ses, and proteases in Erwinia carotovora subsp. carotovora in the absence of the starvation/cell densitysensing signal, N-(3-oxohexanoyl)-L-homoserine lactone. AppL Environ. Microbiol. 6/ 1959 (1995). 

Eberl L, Winson MK, Sternberg C, Stewart GSAB, Christiansen G, Chhabra SR, Bycroft B, Williams P, Molin S and Givskov M. 1996. Involvement of /V-acyl-L-homoserine lactone autoinducers in controlling the multicellular behaviour of Serratia liquefaciens. Mol Microbiol 20 127-136. 

H 0 A-butanoyl-L-homoserine lactone, BHL or C4-HSL Aeromomas hydrophila Aeromonas salmonicida Pseudomonas aeruginosa, Serratia liquefaciens Extracellular protease, biofilm formation. Extracellular protease. Virulence factors - alkaline protease, cyanide, elastase, haemolysin, lectins, pyocyanin, rhaminolipid, RpoS Swarming, protease. 

OH 0, v 0 A r-(3-hydroxybutyryl)-L-homoserine lactone, HBHL or 3-OH, C4-HSL Vibrio harveyi Xenorhabdus nematophilus Bioluminescence, polyhydroxybutyrate metabolism. Virulence, extracellular lipase. 

A-octanoyl-L-homoserine lactone, OHL or C8-HSL Vibrio fischeri Ralslonia solanacearum Yersinia pseudotuberculosis Bioluminescence. Swimming motiliy, cell aggregation, biofilm maturation... 

OH 0 j—y N-(3 -hydroxy-7-c w-tetradecenoyl)-L-homoserine lactone, 7A HtDHL or 7A, 3-OH, C4-HSL Rhizobium leguminosarum Rhodobacter sphaeroides Nodulation, growth inhibition, expression of rhizosphere genes, plasmid transfer Community escape... 

The names of AHLs listed in Table 1 are the non-IUPAC description of compounds as N-acyl derivatives of L-homoserine lactone. Alternatively, IUPAC chemical designations for the compounds can be used. These are based on the amide unit as the principal function. Thus AT-(3-oxohexanoyl)-L-homoserine lactone is named as 3-oxo-N-(tetrahydro-2-oxo-3-furanyl)hexanamide. 

Although the most frequently used nomenclature for AHLs was initially based on a 3-5 letter codes based on names e.g. BHL for N-butyryl-L-homo-serine lactone, OHHL for AT-(3-oxohexanoyl)-L-homoserine lactone or OdDHL for N-(3-oxododecanoyl)-L-homoserine lactone, the rapid expansion in the range of AHL molecules discovered has led to changes in this nomenclature. Currently, the accepted abbreviations are a structure-based short-hand notations e.g. C4-HSL for N-butyryl-L-homoserine lactone, 3-oxo-C6-HSL (or 30,C6-HSL) for AT-(3-oxohexanoyl)-L-homoserine lactone or 3-hydroxy-C12-HSL (or 30H,C12-HSL) for N-(3-hydroxydodecanoyl)-L-homoserine lactone. 

Scheme 2 shows the biosynthesis ofN-(3-oxooctanoyl)-L-homoserine lactone by Tral protein from Agrobacterium using 3-oxooctanoyl-ACP, derived from fatty acid metabolism, as a substrate [29, 33]. Recently, the first crystal structure of a LuxI protein homologue [34] has provided new insights into the function of AHL synthases which will aid the design of novel inhibitors of AHL biosynthesis. 

A number of synthetic methods to prepare all the three main classes of AHLs have appeared in the literature. Initially the methods were developed to prepare the authentic AHLs with defined stereochemistry to confirm the identity of the natural signal molecule. Subsequently, when some of these molecules, e.g. AT-(3-oxododecanoyl)-L-homoserine lactone were found to impact on eukaryotic signalling systems [ 16,50-52], detailed studies not only of their preparation but also of their structural analogues were undertaken by many laboratories. 

Frommberger, M., Schmitt-Kopplin, P., Menzinger, F, Albrecht, V, Schmid, M., Eberl, L., Flartmann, A., and Kettrup, A. (2003). Analysis of N-acyl-l-homoserine lactones produced by Burkholderia cepacia with partial filling micellar electrokinetic chromatography-electrospray ionization-ion trap mass spectrometry. Electrophoresis 24, 3067—3074. 

Azetidine-2-carboxylic acid (2) is commercially available. It is readily prepared as the racemate by refluxing 2,4-dibromobutyric acid ester with benzhydrylamine in acetonitrile. If benzyl 2,4-dibromobutyrate is treated with benzhydrylamine, the resulting benzyl TV-benz-hydryl-D,L-azetidine-2-carboxylate is hydrogenolytically processed to D,L-azetidine-2-car-boxylic acid in a one-step reaction. 101,107 Resolution of the racemate can be performed by the method of Vogler 108 via fractional crystallization of the Z-D,L-Aze-OH-H-Tyr-N2H3 salt thereby the salt of the D-imino acid precipitates first from methanol. 96 A stereoselective synthesis of A-tosyl-L-azetidine-2-carboxylic acid can be achieved by a two-step reaction from N-tosyl-L-homoserine lactone. 94 ... 

Bainton, N.J., Stead, P., Chhabra, S.R., Bycroft, B.W., Salmond, GP., Stewart GS.A.B, Williams, P. N-(3-oxohexanoyl)-L-homoserine lactone regulates carbapenem antibiotic production in Erwinia carotovora. Biochem J 1992 288 997-1004. 

Ritchie AJ, Jansson A, Stallberg J, Nilsson P, Lysaght P, Cooley MA (2005) The Pseudomonas aeruginosa quorum-sensing molecule N-3-(oxododecanoyl)-L-homoserine lactone inhibits T-cell differentiation and cytokine production by a mechanism involving an early step in T-cell activation. Infect Immun 73 1648... 

Winson MK, Camara M, Latifi A, Eoglino M, Chhabra SR, Daykin M, Bally M, Chapon V, Salmond GP, Bycroft BW, et al. Multiple N-acyl-L-homoserine lactone signal molecules regulate production of virulence determinants and secondary metabolites in Pseudomonas aeruginosa. Proc. Natl. Acad. Sci. U.S.A. 1995 92 9427-9431. 

Miyairi S, Tateda K, Euse ET, Ueda C, Saito H, Takabatake T, Ishii Y, Horikawa M, Ishiguro M, Standiford TJ, et al. Immunization with 3-oxododecanoyl-L-homoserine lactone-protein conjugate protects mice from lethal Pseudomonas aeruginosa lung infection. J. Med. Microbiol. 2006, 55 1381—1387. 

Lactonase W-3-oxooctanoyl l-homoserine lactone (0.7 x 10 ) Lactonase W-3-oxooctanoyl l-homoserine lactone (0.55 x 10 ) Lactonase W-3-oxooctanoyl l-homoserine lactone (>10 )... 

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