L-Homoserine

Refs. 21, 22, 155. Abbreviations AHV, a-amino-(3-hydroxyvaleric acid Horn, L-homoserine AEG, (3 -(2-aminoethyl)-L-cysteine ppc, phosphoenolpymvate carboxylase the strain improvement largely depends on the transduction technology sensitive resistant —, auxotroph or deficient , leaky auxotroph +, prototrophic revertant. Table 7. Amino Acid Production from Hydrocarbons ... 

L-cystathionine L-homoserine + L-cysteine cystathionine-y- synthase Streptomyces phaeochromogenes ... 

L-homoserine + thiol (s) cystathionine-a-lyase Ervi carotovora 133... 

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. 

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). 

Boc-O-benzyl-L-homoserine (Boc = t-butoxicarbonyl) was transformed to L-proline methyl ester, and the benzyl ether was removed by hydrogenolysis. The compound was dissolved in 50% acetic acid in methanol and the reaction mixture was degassed by bubbling nitrogen for 5 minutes then 10% Pd/C was added. The system was evacuated for 5 minutes and then pressured to 45 psi of hydrogen for 48 hours at room temperature.66... 

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. 

Differently from serine, ESI-MS analysis of homoserine (HSer) solutions reveals an unusually abundant diprotonated homoserine octamers [(HSer)g-2H], but not the expected monoprotonated [(HSer)g H]" one." A 3/1 mixture of L-serine and L-homoserine yields abundant mixed serine octamers with the incorporation of one or two homoserine molecules into the cluster. CID of the isolated [(Ser)6(HSer)2-H] cluster leads to the preferentially loss of two neutral serine molecules. Homoserine is always retained. The ESl-MS spectral patterns of threonine and allothreonine solutions is similar to that of homoserine. A 1/1 mixture of D-serine and D-threonine yields abundant mixed singly- and doubly-charged octamers incorporating from 2 to 6 threonine molecules. Their relative abundance indicates that threonine may incorporate freely into serine clusters because the additional methyl group does not interfere with the bonding of the cluster. 

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. 

Amino-3-tetrahydrofurancarboxylic acid 17, an oxygen cycloleucine analog, has been synthesized from D,L-homoserine by an intramolecular Mukaiyama aldol condensation in six steps (89TL1181). From o-Thr, l-muscarine 18 was synthesized in eight steps. The synthesis is highly stereoselective (85T5321). 

This pyridoxal-phosphate-dependent enzyme [EC 4.2.99.9], also known as cystathionine y-synthase, catalyzes the reaction of O-succinyl-L-homoserine with L-cysteine to produce cystathionine and succinate. The enzyme can also use hydrogen sulfide and methanethiol as substrates, producing homocysteine and methionine, respectively. In the absence of a thiol, the enzyme can also catalyze a /3,y-elimination reaction to form 2-oxobu-tanoate, succinate, and ammonia. 

SUCCINYL-CoA SYNTHETASE SUCCINYL-CoA SYNTHETASE O-Succinyl-L-homoserine,... 

Canaline is a potent inhibitor of all seven pyridoxal phosphate-containing enzymes studied by Rahiala et (27) but it lacks adverse effects on three ornithine-utiTTzing enzymes lacking a Bg cofactor. Finally, in jack bean, Canavalia ensiformis, ornithine carbamoyl transferase can form 0-ureido-L-homoserine from canaline and carbamoyl phosphate as it does citrulline from ornithine and carbamoyl phosphate. Nevertheless, neither compound inhibited formation of the reaction products (31). 

L-Canavanine sulphate (from jackbean, O-guanidino-L-homoserine) [2219-31-0] M 274.3, m 160-165°(dec), 172°(dec), [ot] 8 5 +19.8° (c 7, H20). Recrystd by dissolving ( lg) in H2O (10ml), and adding with stirring 0.5 to 1.0 vols of 95% EtOH whereby crystals separate. These are collected, washed with Me2CO-EtOH (1 1) and dried over P2O5 in a vacuum. [Hunt and Thompson Biochemical Preparations 13 416 7977 Feacon and Bell BJ 59 221 1955]. 

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