Homoserine lactone

L-Homoserine (2-amino-4-hydroxybutyric acid) [672-15-1] M 119.1, m 203", [cc]d +18.3" (in 2M HCI), pKEst(i) -2.1, pl st(2) 3. Likely impurities are A -chloroacetyl-L-homoserine, N-chloroacetyl-D-homoserine, L-homoserine, homoserine lactone, homoserine anhydride (formed in strong solns of homoserine if slightly acidic). Cyclises to the lactone in strongly acidic soln. Crystd from water by adding 9 volumes of EtOH. 

Bruns A, H Cypionka, J Overmann (2002) Cyclic AMP and acyl homoserine lactones increase cultivation efficiency of heterotrophic bacteria from the Central Baltic Sea. Appl Environ Microbiol 68 3978-3987. 

Figure 1 N-acyl homoserine lactone nucleotides produced by some bacterial species and their phenotype function (From Refs. 34 and 35).

S. Swift, N. J. Bainton, and M. K. Winson, Gram-negative bacterial eommunication by N-acyl homoserine lactones a universal language Trends Microbiol. 2 193 (1994). 

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. 

Fig. 11.1 Characteristic acyl homoserine lactones (AHLs) (a-c) are structurally similar to representative halogenated furanones (d-f) reported from Delisea pulchra (de Nys et al. 1993 Gould et al. 2006)...

Borchardt SA, Allain EJ, Michels JJ, Stearns GW, Kelly RF, McCoy WF (2001) Reaction of acylated homoserine lactone bacterial signaling molecules with oxidized halogen antimicrobials. Appl Environ Microbiol 67 3174-3179... 

Wheeler GL, Tait K, Taylor A, Brownlee C, Joint I (2006) Acyl-homoserine lactones modulate the settlement rate of zoospores of the marine alga Ulva intestinalis via a novel chemokinetic mechanism. Plant Cell Environ 29 608-618... 

Stereochemistry at the a-centre of the homoserine lactone (HSL) ring has been unequivocally established to be l for the V.fischeri autoinducer, AT-(3-oxo-hexanoyl)homoserine lactone and by analogy it is extrapolated that all other natural AHLs have the same configuration. In some cases D-isomers have been synthesised and shown to lack activity [14-17]. 

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. 

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