2.02012-07-30 14:55:30 -06002015-09-17 15:42:05 -0600ECMDB21368M2MDB001764(2R,4S)-2-Methyl-2,3,3,4-tetrahydroxytetrahydrofuran(2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran, also known as autoinducer 2 (AI-2), is a member of the chemical class known as Oxolanes. These are organic compounds containing an oxolane (tetrahydrofuran) ring, which is a saturated aliphatic five-member ring containing one oxygen and five carbon atoms. AI-2 is the R isomer of 2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran, so it can be abbreviated as (R)-THMF. Autoinducer 2 (AI-2), a quorum sensing signaling molecule proposed to be involved in interspecies communication, is produced by many species of gram-negative and gram-positive bacteria including E. coli. (PMID 19636340, 15601708, 18256823) AI-2 is spontaneously derived from 4,5-dihydroxy-2,3-pentanedione that, along with homocysteine, is produced by cleavage of S-adenosylhomocysteine (SAH) and S-ribosylhomocysteine by the Pfs and LuxS enzymes. (PMID 16885435) Both LsrB and Tsr are necessary for sensing AI-2. LsrB binds AI-2 in the periplasm, and Tsr is the L-serine chemoreceptor. (PMID 21097621)(<i>R</i>)-THMF(R)-THMFAI-2AI-2 (salmonella)Auto inducer 2C5H10O5150.13150.052823422(2S,4R)-2-methyloxolane-2,3,3,4-tetrol(2S,4R)-2-methyloxolane-2,3,3,4-tetrolCC1(O)OCC(O)C1(O)OInChI=1S/C5H10O5/c1-4(7)5(8,9)3(6)2-10-4/h3,6-9H,2H2,1H3BVIYGXUQVXBHQS-UHFFFAOYSA-NCytosollogp-1.96logs0.71solubility7.66e+02 g/llogp-1.6pka_strongest_acidic9.16pka_strongest_basic-4iupac(2S,4R)-2-methyloxolane-2,3,3,4-tetrolaverage_mass150.13mono_mass150.052823422smilesCC1(O)OCC(O)C1(O)OformulaC5H10O5inchiInChI=1S/C5H10O5/c1-4(7)5(8,9)3(6)2-10-4/h3,6-9H,2H2,1H3inchikeyBVIYGXUQVXBHQS-UHFFFAOYSA-Npolar_surface_area90.15refractivity30.49polarizability13.34rotatable_bond_count0acceptor_count5donor_count4physiological_charge0formal_charge0Quorum SensingBacterial Autoinducer 2 (AI-2) mediates the quorum sensing 2 system. AI-2 is catalyzed by the luxS enzyme. This enzyme is found in E.coli and S.typhimurium.
In E. coli and most pathogenic bacteria that form AI-2 are spontaneous transformations that include cyclization to (2R,4S)-2-methyl-2,4-dihydroxydihydrofuran-3-one and hydration to the final autoinducer (2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran. This product is released from the cell through the AI-2 transporter (tqsA).
As the level of AI-2 increases, other cells detect it and import it through the autoinducer-2 ABC transporter (lsrACDB). AI-2 is then degraded in the cells by phosphorylating the AI-2 which is then isomerized to P-HPD which follows by the transfer of and acetyl group to coenzyme A and releases dihydroxyacetone phosphatePW000836Signalinginner membrane transportlist of inner membrane transport complexes, transporting compounds from the periplasmic space to the cytosol
This pathway should be updated regularly with the new inner membrae transports addedPW000786Metabolicautoinducer AI-2 biosynthesis IPWY-6153Specdb::MsMs24041Specdb::MsMs24042Specdb::MsMs24043Specdb::MsMs30839Specdb::MsMs30840Specdb::MsMs3084144871926330266CPD-10774Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590.21097882Walters, M., Sircili, M. P., Sperandio, V. (2006). "AI-3 synthesis is not dependent on luxS in Escherichia coli." J Bacteriol 188:5668-5681.16885435Xue, T., Zhao, L., Sun, H., Zhou, X., Sun, B. (2009). "LsrR-binding site recognition and regulatory characteristics in Escherichia coli AI-2 quorum sensing." Cell Res 19:1258-1268.19636340Hegde, M., Englert, D. L., Schrock, S., Cohn, W. B., Vogt, C., Wood, T. K., Manson, M. D., Jayaraman, A. (2011). "Chemotaxis to the quorum-sensing signal AI-2 requires the Tsr chemoreceptor and the periplasmic LsrB AI-2-binding protein." J Bacteriol 193:768-773.21097621Autoinducer 2 import system permease protein lsrCB1XEA2LSRC_ECODHlsrChttp://ecmdb.ca/proteins/B1XEA2.xmlAutoinducer 2 import system permease protein lsrDB1XEA3LSRD_ECODHlsrDhttp://ecmdb.ca/proteins/B1XEA3.xmlAutoinducer 2 import system permease protein lsrDP0AFS1LSRD_ECOLIlsrDhttp://ecmdb.ca/proteins/P0AFS1.xmlAutoinducer 2 import system permease protein lsrCP77672LSRC_ECOLIlsrChttp://ecmdb.ca/proteins/P77672.xmlAutoinducer 2 import ATP-binding protein LsrAP77257LSRA_ECOLIlsrAhttp://ecmdb.ca/proteins/P77257.xmlAutoinducer 2-binding protein LsrBP76142LSRB_ECOLIlsrBhttp://ecmdb.ca/proteins/P76142.xmlWater + (2R,4S)-2-Methyl-2,4-dihydroxydihydrofuran-3-one > (2R,4S)-2-Methyl-2,3,3,4-tetrahydroxytetrahydrofuranRXN-10017(2R,4S)-2-methyl-2,4-dihydroxydihydrofuran-3-one + Water > (2R,4S)-2-Methyl-2,3,3,4-tetrahydroxytetrahydrofuranRXN-10017(2R,4S)-2-Methyl-2,3,3,4-tetrahydroxytetrahydrofuran + Adenosine triphosphate + Water > (2R,4S)-2-Methyl-2,3,3,4-tetrahydroxytetrahydrofuran + ADP + Phosphate + Hydrogen ionTRANS-RXN0-454(2R,4S)-2-Methyl-2,3,3,4-tetrahydroxytetrahydrofuran + Adenosine triphosphate + Water > (2R,4S)-2-Methyl-2,3,3,4-tetrahydroxytetrahydrofuran + ADP + Phosphate + Hydrogen ionTRANS-RXN0-454(2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran + Adenosine triphosphate + (2R,4S)-2-Methyl-2,3,3,4-tetrahydroxytetrahydrofuran > Adenosine diphosphate + Hydrogen ion + (4S)-4-hydroxy-2,3-pentanedione 5-phosphate + ADP + (4S)-4-hydroxy-2,3-pentanedione 5-phosphatePW_R003071(2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran + Phosphoribosyl-ATP + Water + (2R,4S)-2-Methyl-2,3,3,4-tetrahydroxytetrahydrofuran + Phosphoribosyl-ATP > (2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran + Adenosine diphosphate + Hydrogen ion + Pyrophosphate + ADPPW_RCT000124