Lysine Metabolic Pathway Research Articles

A new strategy to alleviate the obesity induced by endocrine disruptors-A unique lysine metabolic pathway of nanoselenium Siraitia grosvenorii to repair gut microbiota and resist obesity.

Obesity caused by endocrine disruptors (EDCs) has become a hot topic threatening human health. Recently, Nanoselenium Siraitia grosvenorii (NSG) has been shown to have potential health-modulating uses. Based on the results of 16S rRNA sequencing and metabolomics analysis, NSG has the unique function of improving gut microbiota and inhibiting obesity. Specifically, NSG can enhance gut microbiota diversity and change their composition. A significant positive correlation exists between the liver change in lysine and the high-importance dominant species ([Ruminococcus]_gnavus, Alistipes_finegoldii, etc.). NSG metabolites analysis showed that the lysine level increased by 44.45% and showed a significantly negatively correlated with (TG, TC, Leptin, etc.). Significantly, NSG reduces the degradation of lysine metabolism in the liver and inhibits fatty acid β-oxidation. In addition, NSG decreased Acetyl-CoA levels by 24% and regulated the downregulation of TCA genes (CS, Ogdh, Fh1, and Mdh2) and the upregulation of ketone body production genes (BDH1). NSG may have a positive effect on obesity by reducing the participation of Acetyl-CoA in the TCA cycle pathway and enhancing the ketogenic conversion of Acetyl-CoA. In conclusion, the results of this study may provide a new dietary intervention strategy for preventing endocrine disruptor-induced obesity.

Lysine biofortification of crops to promote sustained human health in the 21st century.

Crop biofortification is pivotal in preventing malnutrition, with lysine considered the main limiting essential amino acid (EAA) required to maintain human health. Lysine deficiency is predominant in developing countries where cereal crops are the staple food, highlighting the need for efforts aimed at enriching the staple diet through lysine biofortification. Successful modification of aspartate kinase (AK) and dihydrodipicolinate synthase (DHDPS) feedback inhibition has been used to enrich lysine in transgenic rice plants without yield penalty, while increases in the lysine content of quality protein maize have been achieved via marker-assisted selection. Here, we reviewed the lysine metabolic pathway and proposed the use of metabolic engineering targets as the preferred option for fortification of lysine in crops. Use of gene editing technologies to translate the findings and engineer lysine catabolism is thus a pioneering step forward.

Genetic and molecular determinants of polymicrobial interactions in Fusobacterium nucleatum

A gram-negative colonizer of the oral cavity, Fusobacterium nucleatum not only interacts with many pathogens in the oral microbiome but also has the ability to spread to extraoral sites including placenta and amniotic fluid, promoting preterm birth. To date, however, the molecular mechanism of interspecies interactions-termed coaggregation-by F. nucleatum and how coaggregation affects bacterial virulence remain poorly defined. Here, we employed genome-wide transposon mutagenesis to uncover fusobacterial coaggregation factors, revealing the intertwined function of a two-component signal transduction system (TCS), named CarRS, and a lysine metabolic pathway in regulating the critical coaggregation factor RadD. Transcriptome analysis shows that CarR modulates a large regulon including radD and lysine metabolic genes, such as kamA and kamD, the expression of which are highly up-regulated in the ΔcarR mutant. Significantly, the native culture medium of ΔkamA or ΔkamD mutants builds up abundant amounts of free lysine, which blocks fusobacterial coaggregation with streptococci. Our demonstration that lysine-conjugated beads trap RadD from the membrane lysates suggests that lysine utilizes RadD as its receptor to act as a metabolic inhibitor of coaggregation. Lastly, using a mouse model of preterm birth, we show that fusobacterial virulence is significantly attenuated with the ΔkamA and ΔcarR mutants, in contrast to the enhanced virulence phenotype observed upon diminishing RadD (ΔradD or ΔcarS mutant). Evidently, F. nucleatum employs the TCS CarRS and environmental lysine to modulate RadD-mediated interspecies interaction, virulence, and nutrient acquisition to thrive in the adverse environment of oral biofilms and extraoral sites.

ITRAQ analysis reveals the effect of gabD and sucA gene knockouts on lysine metabolism and crystal protein formation in Bacillus thuringiensis

Lysine metabolism plays an important role in the formation of the insecticidal crystal proteins of Bacillus thuringiensis (Bt). The genes lam, gabD and sucA encode three key enzymes of the lysine metabolic pathway in Bt4.0718. The lam gene mainly affects the cell growth at stable period, negligibly affected sporulation and insecticidal crystal protein (ICP) production. While, the deletion mutant strains of the gabD and sucA genes showed that the growth, sporulation and crystal protein formation were inhibited, cells became slender, and insecticidal activity was significantly reduced. iTRAQ proteomics and qRT-PCR used to analyse the differentially expressed protein (DEP) between the two mutant strains and the wild type strain. The functions of DEPs were visualized and statistically classified, which affect bacterial growth and metabolism by regulating biological metabolism pathways: the major carbon metabolism pathways, amino acid metabolism, oxidative phosphorylation pathways, nucleic acid metabolism, fatty acid synthesis and peptidoglycan synthesis. The gabD and sucA genes in lysine metabolic pathway are closely related to the sporulation and crystal proteins formation. The effects of DEPs and functional genes on basic cellular metabolic pathways were studied to provide new strategies for the construction of highly virulent insecticidal strains, the targeted transformation of functional genes.

Transcriptome Analysis and Expression of Selected Cationic Amino Acid Transporters in the Liver of Broiler Chicken Fed Diets with Varying Concentrations of Lysine.

Amino acids are known to play a key role in gene expression regulation. Amino acid signaling is mediated via two pathways: the mammalian target of rapamycin complex 1 (mTORC1) and the amino acid responsive (AAR) pathways. Cationic amino acid transporters (CATs) are crucial in these pathways due to their sensing, signaling and transport functions. The availability of certain amino acids plays a key role in the intake of other amino acids, hence affecting growth in young birds. However, the specific mechanism for regulating lysine transport for growth is not clear. In this study, we analyze the transcriptome profiles and mRNA expression of selected cationic amino acid transporters in the livers of broilers fed low and high lysine diets. Birds consumed high-lysine (1.42% lysine) or low-lysine (0.85% lysine) diets while the control group consumed 1.14% lysine diet. These concentrations of lysine represent 125% (high lysine), 75% (low lysine) and 100% (control), respectively, of the National Research Council’s (NRC) recommendation for broiler chickens. After comparing the two groups, 210 differentially expressed genes (DEGs) were identified (fold change >1 and false discovery rate (FDR) <0.05). When comparing the high lysine and the low lysine treatments, there were 67 upregulated genes and 143 downregulated genes among these DEGs. Analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Gene Ontology (GO) enrichment analysis show that cellular growth, lipid metabolism and lysine metabolism pathways were among the significantly enriched pathways. This study contributes to a better understanding of the potential molecular mechanisms underlying the correlation between lysine intake, body weight gain (BWG) and feed intake (FI) in broiler chickens. Moreover, the DEGs obtained in this study may be used as potential candidate genes for further investigation of broiler growth customized responses to individualized nutrients such as amino acids.

Feeding Strategy of Required Components by Metabolic Engineering Approach in a Lysine Production Process

A metabolic reaction model was developed for on-line analysis of mole flux distribution in lysine metabolic pathway of Corynebacterium glutamicum AJ-3462 which was a leucine auxotroph mutant. The physiological states of the microorganisms were recognized based on the estimated mole flux distribution. In order to elongate the fermentation time keeping lysine productivity and production yield at high levels, effect of leucine addition on the mole flux distribution was analyzed. The intermittently addition strategy of leucine was developed based on the changes in the cell activities with respect to growth and lysine synthesis. Interval time of intermittent addition was changed from 30 h to 24 h when a decrease of cell activity was recognized. As the result, the fermentation time was elongated to 174 h, and lysine productivity and total molar production yield of lysine from glucose became 0.104 g/l/h and 29.2 %, respectively.

Lysine metabolism in the rat brain: the pipecolic acid-forming pathway.

Abstract—Employing both the intraventricular and intraperitoneal injection techniques, 14C‐l‐lysine at non‐overloading concentrations was found to be metabolized to l‐14C‐pipecolic acid at significantly high levels in the rat. Labeled pipecolic acid in the brain and liver was only found at rather low levels 24 h after intraperitoneal administration of 14C‐l‐lysine regardless of non‐labeled lysine metabolite overload. A marked enhancement of pipecolic acid labeling was only found in the brain when 14C‐l‐lysine was intraventricularly administered to animals under various lysine metabolite overloads. While overloading doses of non‐labeled saccharopine or α‐aminoadipate did not significantly alter the labeling patterns of pipecolic acid in the brain, liver or urine when 14C‐l‐lysine was intraperitoneally administered, pipecolate overloading markedly reduced labeled pipecolic acid levels in the brain, liver and urine. These results indicate: pipecolic acid formation is subject to product inhibition, and saccharopine is not in the pathway of pipecolic acid synthesis from l‐lysine. The labeling pattern of lysine metabolites was not significantly affected by the overloading injection of pipecolic acid when 14C‐l‐lysine was intraventricularly administered suggesting a blood‐brain barrier for pipecolate. Besides 14C‐pipecolic acid, labeled α‐aminoadipic acid was also found at significant levels mostly in the brain. Labeled saccharopine was not detected in any tissues or urine samples analyzed. The 14C‐l‐lysine metabolic pattern of the newborn rats did not seem to be any different from the adult rats, i.e. labeled pipecolic acid was also detected in substantial quantities in the brain, liver and urine 5 h after injection. 14C‐d‐Lysine was mainly metabolized to l‐14C‐pipecolic acid through either route of administration. These experimental evidences indicate that the pipecolic acid‐forming pathway is a significant route for lysine metabolism in the rat, and that the rat brain probably utilizes this pathway mainly for lysine metabolism. The present study also discusses the potential neurological significance of the pipecolic acid pathway in relation to the major lysine metabolic pathway (the saccharopine pathway).