Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.1.14 (SPS)
 813 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolic diversity is an important factor during microbial adaptation to different environments. Among metabolic processes, amino acid biosynthesis has been demonstrated to be relevant for survival for many microbial pathogens, whereas the association between pathogenesis and amino acid uptake and recycling are less well-established. Cryptococcus neoformans is an opportunistic fungal pathogen with many habitats. As a result, it faces frequent metabolic shifts and challenges during its life cycle. Here we studied the C. neoformans tryptophan biosynthetic pathway and found that the pathway is essential. RNAi indicated that interruptions in the biosynthetic pathway render strains inviable. However, auxotroph complementation can be partially achieved by tryptophan uptake when a non preferred nitrogen source and lower growth temperature are applied, suggesting that amino acid permeases may be the target of nitrogen catabolism repression (NCR). We used bioinformatics to search for amino acid permeases in the C. neoformans and found eight potential global permeases (AAP1 to AAP8). The transcriptional profile of them revealed that they are subjected to regulatory mechanisms which are known to respond to nutritional status in other fungi, such as (i) quality of nitrogen (Nitrogen Catabolism Repression, NCR) and carbon sources (Carbon Catabolism Repression, CCR), (ii) amino acid availability in the extracellular environment (SPS-sensing) and (iii) nutritional deprivation (Global Amino Acid Control, GAAC). This study shows that C. neoformans has fewer amino acid permeases than other model yeasts, and that these proteins may be subjected to complex regulatory mechanisms. Our data suggest that the C. neoformans tryptophan biosynthetic pathway is an excellent pharmacological target. Furthermore, inhibitors of this pathway cause Cryptococcus growth arrest in vitro.
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PMID:The Role of Amino Acid Permeases and Tryptophan Biosynthesis in Cryptococcus neoformans Survival. 2616 77

Grafting has been reported as a factor that influences fruit quality. However, a comprehensive study of the metabolic profile related to fruit quality and the underlying molecular mechanism in grafted watermelon has not been carried out. Metabolomics and transcriptome analysis were performed on both pumpkin-grafted watermelon and ungrafted watermelon at different developmental stages. In total, 56 primary metabolites were identified with either high or low abundance between ungrafted and pumpkin-grafted watermelon. The results indicated that ornithine, arginine, lysine (amino acids), glucose, sucrose, glucosamine (sugars), malic acid, fumaric acid and succinic acid (organic acids) were among the dominant metabolites influencing fruit quality. Additionally, comparative RNA sequence analysis on grafted and ungrafted watermelon yielded 729, 174, 128 and 356 differentially expressed genes at 10, 18, 26 and 34 days after pollination (DAP), respectively. Functional annotations of these genes indicated that grafting significantly altered the biological and metabolic processes related to fruit quality. Our comparative metabolomics and transcriptome analysis revealed that FBA2, FK, SuSy, SPS, IAI, AI and sugar transporter gene (SWT3b) might play a central role in the accumulation of glucose and sucrose, whereas higher malic acid content was attributed to high down regulation of ALMT13 and ALMT8 in pumpkin-grafted watermelon. Changes in the ornithine, glutamine, alanine, tyrosine, valine, asparagine, phenylalanine, arginine and tryptophan contents were consistent with the transcript level of their metabolic genes such as NAOD, GS, AGT, TaT, aDH1, OGDH, aDC, 4CL 1, PaL, CaT and two nitrate transporter genes (NRT1) in pumpkin-grafted watermelon. This study provides the basis for understanding the graft-responsive changes in the metabolic profile and regulatory mechanism related to fruit quality.
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PMID:Comparative analysis of primary metabolites and transcriptome changes between ungrafted and pumpkin-grafted watermelon during fruit development. 3193 3