Genome-wide analysis of lysine catabolism in bacteria reveals new connections with osmotic stress resistance

Abstract

Lysine is catabolized via the saccharopine pathway in plants and mammals. In this pathway, lysine is converted to a-aminoadipic-d-semialdehyde (AASA) by lysine-ketoglutarate reductase/ saccharopine dehydrogenase (LKR/SDH); thereafter, AASA is converted to aminoadipic acid (AAA) by a-aminoadipic-d-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.

A Connection between Lysine and Serotonin Metabolism in Rice Endosperm

“…418 Kiyota et al, 2015). In bacteria, the saccharopine pathway is associated with stress 419 responses (Less et al, 2011;Neshich et al, 2013). In Arabidopsis, 2-aminoadipate and 420 pipecolate can induce JA accumulation and prime the plant for effective local resistance 421 induction (Návarová., et al, 2012).…”

Engineering Corynebacterium glutamicum for fast production of l-lysine and l-pipecolic acid

“…L-Lysine can be oxidatively deaminated by L-lysine 6-dehydrogenase to yield α-aminoadipic semialdehyde, which after spontaneous cyclization to 1-piperidine 6-carboxylic acid can be reduced by pyrroline 5-carboxylate reductase to L-PA. While C. glutamicum possesses pyrroline 5-carboxylate reductase ProC (Ankri et al 1996), corynebacterial genomes lack genes encoding L-lysine 6-dehydrogenase (Neshich et al 2013). Accordingly, a vector for overexpression of endogenous proC and for expression of heterologous L-lysine 6-dehydrogenase gene lysDH from S. pomeroyi under the control of the constitutive C. glutamicum promoter pTuf was constructed and used to transform GRLys1(pEKEx3), GRLys1ΔsugR(pEKEx3-IolTBest), and GRLys1ΔsugRΔldhA(pEKEx3-IolTBest).…”

“…L-lysine can be converted to other value-added compounds such as the diamine cadaverine (Mimitsuka et al 2007;Tateno et al 2009;Kind et al 2014;Oh et al 2015;Shimizu 2013;Leßmeier et al 2015), 5-aminovalerate (5AVA) (Park et al 2013) and L-PA (Fujii et al 2002;Gatto et al 2006;Neshich et al 2013). C. glutamicum has been engineered for cadaverine production but not for production of L-PA.…”

“…(1) L-lysine cyclodeaminase (LCD) from streptomycetes such as S. hygroscopicus that produce polyketide immunosuppressants such as rapamycin or meridiamycin (Molnár et al 1996); (2) L-lysine 6-aminotransferase (LAT) from Flavobacterium lutencens (Soda et al 1968); and (3) L-lysine 6-dehydrogenase e.g., from Agrobacterium tumefaciens (Misono et al 1989) or from Silicibacter pomeroyi (Neshich et al 2013) (Fig. 1).…”

“…Furthermore, L-lysine can be converted to AASA via saccharopine by L-lysine α-ketoglutarate reductase and saccharopine dehydrogenase from Rizoctonia leguminicola (Wickwire et al 1990). L-PA accumulated intracellularly when Escherichia coli overproducing L -lysine 6-dehydrogenase from S. pomeroyi was grown in L-lysine-containing media (Neshich et al 2013). L-PA was produced from L-lysine in biotransformations with E. coli overproducing either L-lysine α-oxidase from Scomber japonicus (Tani et al 2015) or LAT (Fujii et al 2002).…”