Lysine is catabolized via the saccharopine pathway in plants and mammals. In this pathway, lysine is converted to -aminoadipic-δ-semialdehyde (AASA) by lysine-ketoglutarate reductase/saccharopine dehydrogenase (LKR/SDH); thereafter, AASA is converted to aminoadipic acid (AAA) by -aminoadipic-δ- semialdehyde dehydrogenase (AASADH). Here, we investigate the occurrence, genomic organization and functional role of lysine catabolic pathways among prokaryotes. Surprisingly, only 27 species of the 1478 analyzed contain the lkr and sdh genes, whereas 323 species contain aasadh orthologs. A sdh-related gene, identified in 159 organisms, was frequently found contiguously to an aasadh gene. this gene, annotated as lysine dehydrogenase (lysdh), encodes LYSDH an enzyme that directly converts lysine to AASA. Pipecolate oxidase (PIPOX) and lysine-6-aminotransferase (LAT), that converts lysine to AASA, were also found associated with aasadh. Interestingly, many lysdh-aasadh-containing organisms live under hyperosmotic stress. To test the role of the lysine-to-AASA pathways in the bacterial stress response, we subjected Silicibacter pomeroyi to salt stress. All but lkr, sdh, lysdh and aasadh were upregulated under salt stress conditions. In addition, lysine-supplemented culture medium increased the growth rate of S. pomeroyi under high-salt conditions and induced high-level expression of the lysdh-aasadh operon. Finally, transformation of Escherichia coli with the S. pomeroyi lysdh-aasadh operon resulted in increased salt tolerance. the transformed E. coli accumulated high levels of the compatible solute pipecolate, which may account for the salt resistance. these findings suggest that the lysine-to-AASA pathways identified in this work may have a broad evolutionary importance in osmotic stress resistance. © 2013 International Society for Microbial Ecology All rights reserved.71224002410Alexander, D.C., Anders, C.L., Lee, L., Jensen, S.E., Pcd mutants of Streptomyces clavuligerus still produce cephamycin C (2007) Journal of Bacteriology, 189 (16), pp. 5867-5874. , DOI 10.1128/JB.00712-07Allocati, N., Federici, L., Masulli, M., Di Ilio, C., Glutathione transferases in bacteria (2009) FEBS J, 276, pp. 58-75Altschul, S.F., Madden, T.L., Schaffer, A.A., Zhang, J., Zhang, Z., Miller, W., Lipman, D.J., Gapped BLAST and PSI-BLAST: A new generation of protein database search programs (1997) Nucleic Acids Research, 25 (17), pp. 3389-3402. , DOI 10.1093/nar/25.17.3389Anton, J., Oren, A., Benlloch, S., Rodriguez-Valera, F., Amann, R., Rossello-Mora, R., Salinibacter ruber Gen. Nov., Sp. Nov., A novel, extremely halophilic member of the Bacteria from saltern crystallizer ponds (2002) International Journal of Systematic and Evolutionary Microbiology, 52 (2), pp. 485-491Arruda, P., Kemper, E.L., Papes, F., Leite, A., Regulation of lysine catabolism in higher plants (2000) Trends in Plant Science, 5 (8), pp. 324-330. , DOI 10.1016/S1360-1385(00)01688-5Arruda, P., Neshich, I.P., Nutritional rich and stress tolerant crops by saccharopine pathway manipulation (2012) Food Energy Sec, 2, pp. 1-7Betts, J.C., Lukey, P.T., Robb, L.C., McAdam, R.A., Duncan, K., Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling (2002) Molecular Microbiology, 43 (3), pp. 717-731. , DOI 10.1046/j.1365-2958.2002.02779.xBrocker, C., Lassen, N., Estey, T., Pappa, A., Cantore, M., Orlova, V., Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress (2010) J Biol Chem, 285, pp. 18452-18463Buchanan, C.D., Lim, S., Salzman, R.A., Kagiampakis, I., Morishige, D.T., Weers, B.D., Klein, R.R., Mullet, J.E., Sorghum bicolor's transcriptome response to dehydration, high salinity and ABA (2005) Plant Molecular Biology, 58 (5), pp. 699-720. , DOI 10.1007/s11103-005-7876-2Delano, W.L., (2002) The PyMOL Molecular Graphics System, , Delano Scientific: San Carlos, CA, USADelauney, A.J., Hu, C.-A.A., Kishor, P.B.K., Verma, D.P.S., Cloning of ornithine δ-aminotransferase cDNA from Vigna aconitifolia by trans-complementation in Escherichia coli and regulation of proline biosynthesis (1993) Journal of Biological Chemistry, 268 (25), pp. 18673-18678Deleu, C., Coustaut, M., Niogret, M.-F., Larher, F., Three new osmotic stress-regulated cDNAs identified by differential display polymerase chain reaction in rapeseed leaf discs (1999) Plant, Cell and Environment, 22 (8), pp. 979-988. , DOI 10.1046/j.1365-3040.1999.00471.xEduard, A.S., Jakobs, C., Metabolism of lysine in a-aminoadipic semialdehyde dehydrogenase- deficient fibroblasts: Evidence for an alternative pathway of pipecolic acid formation (2010) FEBS Lett, 584, pp. 181-186Feller, A., Dubois, E., Ramos, F., Pierard, A., Repression of the genes for lysine biosynthesis in Saccharomyces cerevisiae is caused by limitation of Lys14-dependent transcriptional activation (1994) Molecular and Cellular Biology, 14 (10), pp. 6411-6418Fujii, T., Mukaihara, M., Agematu, H., Tsunekawa, H., Biotransformation of L-lysine to L-pipecolic acid catalyzed by L-lysine 6-aminotransferase and pyrroline-5-carboxylate reductase (2002) Bioscience, Biotechnology and Biochemistry, 66 (3), pp. 622-627Fujii, T., Narita, T., Agematu, H., Agata, N., Isshiki, K., Characterization of L-lysine 6-aminotransferase and its structural gene from Flavobacterium lutescens IFO3084 (2000) J Biochem, 128, pp. 391-397Fukutoku, F., Yamada, Y., Sources of proline-nitrogen in water-stressed soybean (Glycine max L.) i Protein metabolism and proline accumulation (1981) Plant Cell Physiol, 22, pp. 1397-1404Gebhard, S., Hümpel, A., McLellan, A.D., Cook, G.M., The alternative sigma factor SigF of Mycobacterium smegmatis is required for survival of heat shock, acidic pH and oxidative stress (2008) Microbiology, 154, pp. 2786-2795Goas, G., Goas, M., Larher, F., Formation de l?acide pipecolique chez Triglochin maritime (1975) Can. J. Bot, 54, pp. 1221-1227Gouesbet, G., Blanco, C., Hamelin, J., Bernard, T., Osmotic adjustment in Brevibacterium ammoniagenes: Pipecolic acid accumulation at elevated osmolalities (1992) Microbiology, 138, pp. 959-965Gouesbet, G., Jebbar, M., Talibart, R., Bernard, T., Blanco, C., Pipecolic acid is an osmoprotectant for Escherichia coli taken up by the general osmoporters ProU and ProP (1994) Microbiology, 140 (9), pp. 2415-2422Gratao, P.L., Polle, A., Lea, P.J., Azevedo, R.A., Making the life of heavy metal-stressed plants a little easier (2005) Functional Plant Biology, 32 (6), pp. 481-494. , DOI 10.1071/FP05016Guerrero, F.D., Jones, J.T., Mullet, J.E., Turgor-responsive gene transcription and RNA levels increase rapidly when pea shoots are wilted sequence and expression of three inducible genes (1990) Plant Mol Biol, 15, pp. 11-26Jefferies, R.L., Rudmik, T., Dillon, E.M., Responses of halophytes to high salinities and low water potentials (1979) Plant Physiol, 64, pp. 989-994Jones, D.T., Taylor, W.R., Thornton, J.M., The rapid generation of mutation data matrices from protein sequences (1992) Comput Appl Biosci, 8, pp. 275-282Karlsson, J.O., Ostwald, K., Kabjorn, C., Andersson, M., A method for protein assay in Laemmli buffer (1994) Analytical Biochemistry, 219 (1), pp. 144-146. , DOI 10.1006/abio.1994.1243Kirch, H.-H., Schlingensiepen, S., Kotchoni, S., Sunkar, R., Bartels, D., Detailed expression analysis of selected genes of the aldehyde dehydrogenase (ALDH) gene superfamily in Arabidopsis thaliana (2005) Plant Molecular Biology, 57 (3), pp. 315-332. , DOI 10.1007/s11103-004-7796-6Lima, T., Auchincloss, A.H., Coudert, E., Keller, G., Michoud, K., Rivoire, C., HAMAP: A database of completely sequenced microbial proteome sets and manually curated microbial protein families in Uni- ProtKB/Swiss-Prot (2009) Nucleic Acids Res, 37, pp. D471-D478Misono, H., Nagasaki, S., Occurrence of l-lysine ε-dehydrogenase in Agrobacterium tumefaciens (1982) Journal of Bacteriology, 150 (1), pp. 398-401Moulin, M., Deleu, C., Larher, F., Bouchereau, A., The lysine-ketoglutarate reductase-saccharopine dehydrogenase is involved intheosmo-induced synthesis ofpipecolic acid inrapeseedleaftissues (2006) Plant Physiology and Biochemistry, 44 (7-9), pp. 474-482. , DOI 10.1016/j.plaphy.2006.08.005, PII S0981942806001082Moulin, M., Deleu, C., Larher, F., L-Lysine catabolism is osmo-regulated at the level of lysine-ketoglutarate reductase and saccharopine dehydrogenase in rapeseed leaf discs (2000) Plant Physiol Biochem, 38, pp. 577-585Papes, F., Kemper, E.L., Cord-Neto, G., Langone, F., Arruda, P., Lysine degradation through the saccharopine pathway in mammals: Involvement of both bifunctional and monofunctional lysine-degrading enzymes in mouse (1999) Biochemical Journal, 344 (2), pp. 555-563. , DOI 10.1042/0264-6021:3440555Peisach, J., Strecker, H.J., The interconversion of glutamic acid and proline. V. The reduction of delta 1-pyrroline-5-carboxylic acid to proline (1962) J Biol Chem, 237, pp. 2255-2260Revelles, O., Espinosa-Urgel, M., Fuhrer, T., Sauer, U., Ramos, J.L., Multiple and interconnected pathways for l-lysine catabolism in Pseudomonas putida KT2440 (2005) Journal of Bacteriology, 187 (21), pp. 7500-7510. , DOI 10.1128/JB.187.21.7500-7510.2005Rodrigues, S.M., Andrade, M.O., Gomes, A.P.S., DaMatta, F.M., Baracat-Pereira, M.C., Fontes, E.P.B., Arabidopsis and tobacco plants ectopically expressing the soybean antiquitin-like ALDH7 gene display enhanced tolerance to drought, salinity, and oxidative stress (2006) Journal of Experimental Botany, 57 (9), pp. 1909-1918. , DOI 10.1093/jxb/erj132Serrano, G.C., Silva Figueira, T.R., Kiyota, E., Zanata, N., Arruda, P., Lysine degradation through the saccharopine pathway in bacteria: LKR and SDH in bacteria and its relationship to the plant and animal enzymes (2012) FEBS Lett, 586, pp. 905-911Stroeher, V.L., Boothe, J.G., Good, A.G., Molecular cloning and expression of a turgor-responsive gene in Brassica napus (1995) Plant Mol Biol, 27, pp. 541-551Tamura, K., Peterson, D., Peterson, N., Stecher, G., Nei, M., Kumar, S., MEGA5: Molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods (2011) Mol Biol Evol, 28, pp. 2731-2739Veal, E.A., Toone, W.M., Jones, N., Morgan, B.A., Distinct roles for glutathione S-transferases in the oxidative stress response in Schizosaccharomyces pombe (2002) J Biol Chem, 277, pp. 35523-35531Yee, L., Blanch, H.W., Recombinant trypsin production in high cell density fed-batch cultures in Escherichia coli (1993) Biotechnology and Bioengineering, 41 (8), pp. 781-790Yoneda, K., Fukuda, J., Sakuraba, H., Ohshima, T., First crystal structure of L-lysine 6-dehydrogenase as an NAD-dependent amine dehydrogenase (2010) J Biol Chem, 285, pp. 8444-8453Zeigler, D.R., Gene sequences useful for predicting relatedness of whole genomes in bacteria (2003) International Journal of Systematic and Evolutionary Microbiology, 53 (6), pp. 1893-1900. , DOI 10.1099/ijs.0.02713-0