scholarly journals Evolution of a xenobiotic degradation pathway: formation and capture of the labile phthaloyl-CoA intermediate during anaerobic phthalate degradation

2018 ◽  
Vol 108 (6) ◽  
pp. 614-626 ◽  
Author(s):  
Mario Mergelsberg ◽  
Valentin Egle ◽  
Matthias Boll
Keyword(s):  
Degradation Pathway ◽  
Pathway Formation ◽  
Xenobiotic Degradation

Mitochondria Associated Degradation Pathway (MAD) Function Beyond the Outer Membrane

2019 ◽  
Author(s):  
Pin-Chao Liao ◽  
Dana Alessi Wolken ◽  
Edith Serrano ◽  
Pallavi Srivastava ◽  
Liza A. Pon
Keyword(s):  
Outer Membrane ◽  
Degradation Pathway

Corticosteroid Catabolism by Klebsiella pneumoniae as a Possible Mechanism for Increased Pneumonia Risk

2019 ◽  
Vol 20 (4) ◽  
pp. 309-316 ◽  
Author(s):  
Pritam Chattopadhyay ◽  
Goutam Banerjee
Keyword(s):  
Amino Acid ◽  
Klebsiella Pneumoniae ◽  
Kegg Pathway ◽  
Degradation Pathway ◽  
Amino Acid Sequences ◽  
Biological Mechanism ◽  
Clinical Strains ◽  
Catabolism Pathway ◽  
Steroid Catabolism ◽  
Nutrition Source

Background: Several strains of Klebsiella pneumoniae are responsible for causing pneumonia in lung and thereby causing death in immune-suppressed patients. In recent year, few investigations have reported the enhancement of K. pneumoniae population in patients using corticosteroid containing inhaler. Objectives: The biological mechanism(s) behind this increased incidence has not been elucidated. Therefore, the objective of this investigating was to explore the relation between Klebsiella pneumoniae and increment in carbapenamase producing Enterobacteriaceae score (ICS). Methods: The available genomes of K. pneumoniae and the amino acid sequences of steroid catabolism pathway enzymes were taken from NCBI database and KEGG pathway tagged with UniPort database, respectively. We have used different BLAST algorithms (tBLASTn, BLASTp, psiBLAST, and delBLAST) to identify enzymes (by their amino acid sequence) involved in steroid catabolism. Results: A total of 13 enzymes (taken from different bacterial candidates) responsible for corticosteroid degradation have been identified in the genome of K. pneumoniae. Finally, 8 enzymes (K. pneumoniae specific) were detected in four clinical strains of K. pneumoniae. This investigation intimates that this ability to catabolize corticosteroids could potentially be one mechanism behind the increased pneumonia incidence. Conclusion: The presence of corticosteroid catabolism enzymes in K. pneumoniae enhances the ability to utilize corticosteroid for their own nutrition source. This is the first report to demonstrate the corticosteroid degradation pathway in clinical strains of K. pneumoniae.

UV/H2O2 oxidation of tri(2-chloroethyl) phosphate: Intermediate products, degradation pathway and toxicity evaluation

2020 ◽  
Vol 98 ◽  
pp. 55-61 ◽  
Author(s):  
Qiuyi Ji ◽  
Huan He ◽  
Zhanqi Gao ◽  
Xiaohan Wang ◽  
Shaogui Yang ◽  
...  
Keyword(s):  
Degradation Pathway ◽  
Toxicity Evaluation ◽  
Intermediate Products ◽  
H2o2 Oxidation

scholarly journals Further Studies on the 3-Ketosteroid 9α-Hydroxylase of Rhodococcus ruber Chol-4, a Rieske Oxygenase of the Steroid Degradation Pathway

2021 ◽  
Vol 9 (6) ◽  
pp. 1171
Author(s):  
Sara Baldanta ◽  
Juana María Navarro Llorens ◽  
Govinda Guevara
Keyword(s):  
Cholesterol Metabolism ◽  
Genetic Regulation ◽  
Degradation Pathway ◽  
Rhodococcus Ruber ◽  
Promoter Regions ◽  
Steroid Nucleus ◽  
Steroid Substrate ◽  
Fine Regulation ◽  
Rieske Oxygenase ◽  
Steroid Catabolism

The biochemistry and genetics of the bacterial steroid catabolism have been extensively studied during the last years and their findings have been essential to the development of biotechnological applications. For instance, metabolic engineering of the steroid-eater strains has allowed to obtain intermediaries of industrial value. However, there are still some drawbacks that must be overcome, such as the redundancy of the steroid catabolism genes in the genome and a better knowledge of its genetic regulation. KshABs and KstDs are key enzymes involved in the aerobic breakage of the steroid nucleus. Rhodococcus ruber Chol-4 contains three kshAs genes, a single kshB gene and three kstDs genes within its genome. In the present work, the growth of R. ruber ΔkshA strains was evaluated on different steroids substrates; the promoter regions of these genes were analyzed; and their expression was followed by qRT-PCR in both wild type and ksh mutants. Additionally, the transcription level of the kstDs genes was studied in the ksh mutants. The results show that KshA2B and KshA1B are involved in AD metabolism, while KshA3B and KshA1B contribute to the cholesterol metabolism in R. ruber. In the kshA single mutants, expression of the remaining kshA and kstD genes is re-organized to survive on the steroid substrate. These data give insight into the fine regulation of steroid genes when several isoforms are present.

scholarly journals Enhanced Autophagic Activity Improved the Root Growth and Nitrogen Utilization Ability of Apple Plants under Nitrogen Starvation

2021 ◽  
Vol 22 (15) ◽  
pp. 8085
Author(s):  
Liuqing Huo ◽  
Zijian Guo ◽  
Qi Wang ◽  
Li Cheng ◽  
Xin Jia ◽  
...  
Keyword(s):  
Transgenic Plants ◽  
Root Growth ◽  
Nitrogen Starvation ◽  
Degradation Pathway ◽  
Physiological Status ◽  
Hydroponic System ◽  
Nitrogen Levels ◽  
Nitrogen Concentrations ◽  
Nitrogen Nutrients ◽  
Autophagic Activity

Autophagy is a conserved degradation pathway for recycling damaged organelles and aberrant proteins, and its important roles in plant adaptation to nutrient starvation have been generally reported. Previous studies found that overexpression of autophagy-related (ATG) gene MdATG10 enhanced the autophagic activity in apple roots and promoted their salt tolerance. The MdATG10 expression was induced by nitrogen depletion condition in both leaves and roots of apple plants. This study aimed to investigate the differences in the growth and physiological status between wild type and MdATG10-overexpressing apple plants in response to nitrogen starvation. A hydroponic system containing different nitrogen levels was used. The study found that the reduction in growth and nitrogen concentrations in different tissues caused by nitrogen starvation was relieved by MdATG10 overexpression. Further studies demonstrated the increased root growth and the higher nitrogen absorption and assimilation ability of transgenic plants. These characteristics contributed to the increased uptake of limited nitrogen nutrients by transgenic plants, which also reduced the starvation damage to the chloroplasts. Therefore, the MdATG10-overexpressing apple plants could maintain higher photosynthetic ability and possess better growth under nitrogen starvation stress.

Targeting E7 antigen to the endoplasmic reticulum degradation pathway promotes a potent therapeutic antitumor effect

2021 ◽  
pp. 1-9
Author(s):  
David Hernán Martínez-Puente ◽  
Rodolfo Garza-Morales ◽  
José Juan Pérez-Trujillo ◽  
Aracely García-García ◽  
Arnulfo Villanueva-Olivo ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Antitumor Effect ◽  
Degradation Pathway ◽  
Therapeutic Antitumor Effect ◽  
E7 Antigen

scholarly journals Identification and characterization of regulatory pathways involved in early flowering in the new leaves of alfalfa (Medicago sativa L.) by transcriptome analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dongmei Ma ◽  
Bei Liu ◽  
Lingqiao Ge ◽  
Yinyin Weng ◽  
Xiaohui Cao ◽  
...  
Keyword(s):  
Medicago Sativa ◽  
Secondary Metabolism ◽  
Flowering Time ◽  
Degradation Pathway ◽  
Early Flowering ◽  
Receptor Kinase ◽  
Leucine Rich Repeat ◽  
Kinase Family ◽  
Pathogenesis Related ◽  
Early Flowering Phenotype

Abstract Background Alfalfa (Medicago sativa L.) is a perennial legume extensively planted throughout the world as a high nutritive value livestock forage. Flowering time is an important agronomic trait that contributes to the production of alfalfa hay and seeds. However, the underlying molecular mechanisms of flowering time regulation in alfalfa are not well understood. Results In this study, an early-flowering alfalfa genotype 80 and a late-flowering alfalfa genotype 195 were characterized for the flowering phenotype. Our analysis revealed that the lower jasmonate (JA) content in new leaves and the downregulation of JA biosynthetic genes (i.e. lipoxygenase, the 12-oxophytodienoate reductase-like protein, and salicylic acid carboxyl methyltransferase) may play essential roles in the early-flowering phenotype of genotype 80. Further research indicated that genes encode pathogenesis-related proteins [e.g. leucine rich repeat (LRR) family proteins, receptor-like proteins, and toll-interleukin-like receptor (TIR)-nucleotide-binding site (NBS)-LRR class proteins] and members of the signaling receptor kinase family [LRR proteins, kinases domain of unknown function 26 (DUF26) and wheat leucine-rich repeat receptor-like kinase10 (LRK10)-like kinases] are related to early flowering in alfalfa. Additionally, those involved in secondary metabolism (2-oxoglutarate/Fe (II)-dependent dioxygenases and UDP-glycosyltransferase) and the proteasome degradation pathway [really interesting new gene (RING)/U-box superfamily proteins and F-box family proteins] are also related to early flowering in alfalfa. Conclusions Integrated phenotypical, physiological, and transcriptomic analyses demonstrate that hormone biosynthesis and signaling pathways, pathogenesis-related genes, signaling receptor kinase family genes, secondary metabolism genes, and proteasome degradation pathway genes are responsible for the early flowering phenotype in alfalfa. This will provide new insights into future studies of flowering time in alfalfa and inform genetic improvement strategies for optimizing this important trait.

scholarly journals DDRE-09. DEVELOPING IDO-PROTACS TO IMPROVE IMMUNOTHERAPEUTIC EFFICACY IN PATIENTS WITH GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii63-ii63
Author(s):  
Lakshmi Bollu ◽  
Derek Wainwright ◽  
Lijie Zhai ◽  
Erik Ladomersky ◽  
Kristen Lauing ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Time Course ◽  
Immune Cell ◽  
Enzyme Inhibitors ◽  
Tumor Development ◽  
Ubiquitin Proteasome System ◽  
Degradation Pathway ◽  
Specific Protein ◽  
Cell Functions

Abstract INTRODUCTION Indoleamine 2,3-dioxygenase 1 (IDO; IDO1) is a rate-limiting enzyme that metabolizes the essential amino acid tryptophan into kynurenine. Recent work by our group has revealed that IDO promotes tumor development and suppresses immune cell functions independent of its enzyme activity. Moreover, pharmacologic IDO enzyme inhibitors that currently serve as the only class of drugs available for targeting immunosuppressive IDO activity, fail to improve the survival of patients with GBM. Here, we developed IDO-Proteolysis Targeting Chimeras (IDO-PROTACs). PROTACs bind to a specific protein and recruit an E3 ubiquitin ligase that enhance proteasome-mediated degradation of the target protein. METHODS A library of ≥100 IDO-PROTACs were developed by joining BMS986205 (IDO binder) with a linker group to various E3-ligase ligands. Western blot analysis of PROTAC-induced IDO degradation was tested in vitro among multiple human and mouse GBM cell lines including U87, GBM6, GBM43 and GL261 along a time course ranging between 1–96 hours of treatment and at varying concentrations. The mechanism of IDO protein degradation was investigated using pharmacologic ligands that inhibit or compete with the proteasome-mediated protein degradation pathway. RESULTS Primary screening identified several IDO-PROTACs with IDO protein degradation potential. Secondary screening showed that our lead compound has a DC50 value of ~0.5µM with an ability to degrade IDO in all GBM cells analyzed, and an initial activity within 12 hours of treatment that extended for up to 96 hours. Mutating the CRBN-binding ligand, pretreatment with the ubiquitin proteasome system inhibitors MG132 or MLN4924 or using unmodified parental compound all inhibited IDO protein degradation. CONCLUSIONS This study developed an initial IDO-PROTAC technology that upon further optimization, can neutralize both IDO enzyme and non-enzyme immunosuppressive effects. When combined with other forms of immunotherapy, IDO-PROTACs have the potential to substantially enhance immunotherapeutic efficacy in patients with GBM.

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