scholarly journals Aminoacyl chain translocation catalysed by a type II thioesterase domain in an unusual non-ribosomal peptide synthetase

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Shan Wang ◽  
William D. G. Brittain ◽  
Qian Zhang ◽  
Zhou Lu ◽  
Ming Him Tong ◽  
...  
Keyword(s):  
Chain Transfer ◽  
Acyl Chain ◽  
Structural Diversity ◽  
Type Ii ◽  
Diverse Range ◽  
Translocation Event ◽  
Peptide Synthetases ◽  
Peptide Synthetase ◽  
Biosynthetic Engineering

AbstractNon-Ribosomal Peptide Synthetases (NRPSs) assemble a diverse range of natural products with important applications in both medicine and agriculture. They consist of several multienzyme subunits that must interact with each other in a highly controlled manner to facilitate efficient chain transfer, thus ensuring biosynthetic fidelity. Several mechanisms for chain transfer are known for NRPSs, promoting structural diversity. Herein, we report the first biochemically characterized example of a type II thioesterase (TEII) domain capable of catalysing aminoacyl chain transfer between thiolation (T) domains on two separate NRPS subunits responsible for installation of a dehydrobutyrine moiety. Biochemical dissection of this process reveals the central role of the TEII-catalysed chain translocation event and expands the enzymatic scope of TEII domains beyond canonical (amino)acyl chain hydrolysis. The apparent co-evolution of the TEII domain with the NRPS subunits highlights a unique feature of this enzymatic cassette, which will undoubtedly find utility in biosynthetic engineering efforts.

scholarly journals Type II thioesterase ScoT is required for coelimycin production by the modular polyketide synthase Cpk of Streptomyces coelicolor A3(2).

2014 ◽  
Vol 61 (1) ◽  
Author(s):  
Magdalena Kotowska ◽  
Jarosław Ciekot ◽  
Krzysztof Pawlik
Keyword(s):  
Culture Medium ◽  
Polyketide Synthase ◽  
Streptomyces Coelicolor ◽  
Acyl Chain ◽  
No Production ◽  
Type I ◽  
Type Ii ◽  
Peptide Synthetases ◽  
Modular Polyketide Synthase ◽  
Editing Enzyme

Type II thioesterases were shown to maintain efficiency of modular type I polyketide synthases and nonribosomal peptide synthetases by removing acyl residues blocking extension modules. We found that thioesterase ScoT from Streptomyces coelicolor A3(2) is required for the production of the yellow-pigmented coelimycin by the modular polyketide synthase Cpk. No production of coelimycin was observed in cultures of scoT disruption mutant. Polyketide production was restored upon complementation with an intact copy of the scoT gene. An enzymatic assay showed that ScoT thioesterase can hydrolyse a 12-carbon acyl chain but the activity is too low to play a role in product release from the polyketide synthase. We conclude that ScoT is an editing enzyme necessary to maintain the activity of polyketide synthase Cpk. We provide a HPLC based method to measure the amount of coelimycin P2 in a culture medium.

scholarly journals Phosphinothricin Tripeptide Synthetases in Streptomyces viridochromogenes Tü494

2005 ◽  
Vol 49 (11) ◽  
pp. 4598-4607 ◽  
Author(s):  
Dirk Schwartz ◽  
Nicolas Grammel ◽  
Eva Heinzelmann ◽  
Ullrich Keller ◽  
Wolfgang Wohlleben
Keyword(s):  
Gene Cluster ◽  
Nonribosomal Peptide Synthetase ◽  
Herbicidal Activity ◽  
Type Ii ◽  
Biosynthesis Gene Cluster ◽  
Nonribosomal Peptide ◽  
Product Release ◽  
Peptide Synthetase ◽  
Biosynthesis Gene

ABSTRACT The tripeptide backbone of phosphinothricin (PT) tripeptide (PTT), a compound with herbicidal activity from Streptomyces viridochromogenes, is assembled by three stand-alone peptide synthetase modules. The enzyme PhsA (66 kDa) recruits the PT-precursor N-acetyl-demethylphosphinothricin (N-Ac-DMPT), whereas the two alanine residues of PTT are assembled by the enzymes PhsB and PhsC (129 and 119 kDa, respectively). During or after assembly, the N-Ac-DMPT residue in the peptide is converted to PT by methylation and deacetylation. Both phsB and phsC appear to be cotranscribed together with two other genes from a single promoter and they are located at a distance of 20 kb from the gene phsA, encoding PhsA, in the PTT biosynthesis gene cluster of S. viridochromogenes. PhsB and PhsC represent single nonribosomal peptide synthetase elongation modules lacking a thioesterase domain. Gene inactivations, genetic complementations, determinations of substrate specificity of the heterologously produced proteins, and comparison of PhsC sequence with the amino terminus of the alanine-activating nonribosomal peptide synthetase PTTSII from S. viridochromogenes confirmed the role of the two genes in the bialanylation of Ac-DMPT. The lack of an integral thioesterase domain in the PTT assembly system points to product release possibly involving two type II thioesterase genes (the1 and the2) located in the PTT gene cluster alone or in conjunction with an as yet unknown mechanism of product release.

The possible role of Saponin in Type-II Diabetes- A review

2020 ◽  
Vol 16 ◽  
Author(s):  
Neeraj Choudhary ◽  
Gopal Lal Khatik ◽  
Ashish Suttee
Keyword(s):  
Secondary Metabolites ◽  
Type Ii Diabetes ◽  
Structural Diversity ◽  
Complete Information ◽  
Current Data ◽  
Type Ii ◽  
Glucose Levels ◽  
Therapeutic Benefits ◽  
The Impact

Background: The possible role of secondary metabolites in the management of diabetes is a great concern and constant discussion. This characteristic seems relevant and should be the subject of thorough discussion with respect to saponin. Objective: Current data mainly focus on the impact of saponin in the treatment of type-II diabetes. The majority of studies emphasis on other secondary metabolites such as alkaloids and flavonoids but very few papers are there representing the possible role of saponin as these papers express the narrow perspective of saponin phytoconstituents but lacking in providing the complete information on various saponin plants. The aim of the study was to summarize all available data concerning the saponin containing plant in the management of type-II diabetes. Methods: All relevant papers on saponin were selected. This review summarizes the saponins isolation method, mechanism of action, clinical significance, medicinal plants and phytoconstituents responsible for producing a therapeutic effect in the management of diabetes. Results: The saponin is of high potential with structural diversity and inhibits diabetic complications along with reducing the hyperglycemia through different mechanisms thereby providing scope for improving the existing therapy and developing the novel medicinal agents for curing diabetes. Conclusion: Saponins having potential therapeutic benefits and are theorized as an alternative medication in decreasing serum blood glucose levels in the patient suffering from diabetes.

scholarly journals Cyclic Lipopeptide Production by Plant-Associated Pseudomonas spp.: Diversity, Activity, Biosynthesis, and Regulation

2006 ◽  
Vol 19 (7) ◽  
pp. 699-710 ◽  
Author(s):  
Jos M. Raaijmakers ◽  
Irene de Bruijn ◽  
Maarten J. D. de Kock
Keyword(s):  
Amino Acids ◽  
Fatty Acid ◽  
Structural Diversity ◽  
Main Mode ◽  
Pseudomonas Spp ◽  
Peptide Synthetases ◽  
Cyclic Lipopeptide ◽  
Peptide Moiety ◽  
Peptide Synthetase ◽  
Signature Sequences

Cyclic lipopeptides (CLPs) are versatile molecules produced by a variety of bacterial genera, including plant-associated Pseudomonas spp. CLPs are composed of a fatty acid tail linked to a short oligopeptide, which is cyclized to form a lactone ring between two amino acids in the peptide chain. CLPs are very diverse both structurally and in terms of their biological activity. The structural diversity is due to differences in the length and composition of the fatty acid tail and to variations in the number, type, and configuration of the amino acids in the peptide moiety. CLPs have received considerable attention for their antimicrobial, cytotoxic, and surfactant properties. For plant-pathogenic Pseudomonas spp., CLPs constitute important virulence factors, and pore formation, followed by cell lysis, is their main mode of action. For the antagonistic Pseudomonas sp., CLPs play a key role in antimicrobial activity, motility, and biofilm formation. CLPs are produced via nonribosomal synthesis on large, multifunctional peptide synthetases. Both the structural organization of the CLP synthetic templates and the presence of specific domains and signature sequences within peptide synthetase genes will be described for both pathogenic and antagonistic Pseudomonas spp. Finally, the role of various genes and regulatory mechanisms in CLP production by Pseudomonas spp., including two-component regulation and quorum sensing, will be discussed in detail.

scholarly journals Modulation of Toxin-Antitoxin System Rnl AB Type II in Phage-Resistant Gammaproteobacteria Surviving Photodynamic Treatment

2018 ◽  
Vol 10 (1) ◽  
pp. 21-28
Author(s):  
Nava Hosseini ◽  
Maryam Pourhajibagher ◽  
Nasim Chiniforush ◽  
Nazanin Hosseinkhan ◽  
Parizad Rezaie ◽  
...  
Keyword(s):  
Phylogenetic Trees ◽  
Bacterial Population ◽  
Defense Mechanism ◽  
Type Ii ◽  
Neighbor Joining ◽  
Photodynamic Treatment ◽  
Diverse Range ◽  
T4 Bacteriophage ◽  
K 12

Type II toxin-antitoxin (TA) systems are the particular type of TA modules which take part in different kinds of cellular actions, such as biofilm formation, persistence, stress endurance, defense of the bacterial cell against multiple phage attacks, plasmid maintenance, and programmed cell death in favor of bacterial population. Although several bioinformatics and Pet lab studies have already been conducted to understand the functionality of already discovered TA systems, still, more work in this area is required. Rnl AB type II TA module, which is composed of RnlA toxin and RnlB antitoxin, is a newly discovered type II TA module which takes part in the defense mechanism against T4 bacteriophage attack in Escherichia coli K-12 strain MH1 that has not been widely studied in other bacteria. Because of the significant role of class Gammaproteobacteriacea in a diverse range of health problems, we chose here to focus on this class to survey the presence of the Rnl AB TA module. For better categorization and description of the distribution of this module in this class of bacteria, the corresponding phylogenetic trees are illustrated here. Neighbor-joining and the maximum parsimony methods were used in this study to take a look at the distribution of domains present in RnlA and RnlB proteins, among members of Gammaproteobacteria. Also, the possible roles of photodynamic therapy (PDT) in providing a substrate for better phage therapy are herein discussed.

Role of hyperglucagonemia in maintenance of increased rates of hepatic glucose output in type II diabetics

Diabetes ◽  
1987 ◽  
Vol 36 (3) ◽  
pp. 274-283 ◽  
Author(s):  
A. D. Baron ◽  
L. Schaeffer ◽  
P. Shragg ◽  
O. G. Kolterman
Keyword(s):  
Type Ii ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Type Ii Diabetics ◽  
Glucose Output

Role of lipid oxidation in pathogenesis of insulin resistance of obesity and type II diabetes

Diabetes ◽  
1987 ◽  
Vol 36 (11) ◽  
pp. 1341-1350 ◽  
Author(s):  
J. P. Felber ◽  
E. Ferrannini ◽  
A. Golay ◽  
H. U. Meyer ◽  
D. Theibaud ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Oxidation ◽  
Type Ii Diabetes ◽  
Type Ii

Exploring the role of identity fusion and group identification in predicting parochialism amongst Indonesian Islamic groups

2019 ◽  
Author(s):  
Christopher Michael Kavanagh ◽  
Susilo Wibisono ◽  
Rohan Kapitány ◽  
Whinda Yustisia ◽  
Idhamsyah Eka Putra ◽  
...  
Keyword(s):  
Group Identification ◽  
Control Sample ◽  
Theoretical Models ◽  
Religious Groups ◽  
Diverse Range ◽  
Beliefs And Practices ◽  
Identity Fusion ◽  
Beliefs And Practice ◽  
Fusion Theory

Indonesia is the most populous Islamic country and as such is host to a diverse range of Islamic beliefs and practices. Here we examine how the diversity of beliefs and practices among Indonesian Muslims relates to group bonding and parochialism. In particular, we examine the predictive power of two distinct types of group alignment, group identification and identity fusion, among individuals from three Sunni politico-religious groups - a fundamentalist group (PKS), a moderate group (NU), and a control sample of politically unaffiliated citizens. Fundamentalists were more fused to targets than moderates or citizens, but contrary to fusion theory, we found across all groups, that group identification (not fusion) better predicted parochialism, including willingness to carry out extreme pro-group actions. We discuss how religious beliefs and practice impact parochial attitudes, as well as the implications for theoretical models linking fusion to extreme behaviour.

scholarly journals New Insights on the Role of TRP Channels in Calcium Signalling and Immunomodulation: Review of Pathways and Implications for Clinical Practice

2021 ◽  
Author(s):  
Saied Froghi ◽  
Charlotte R. Grant ◽  
Radhika Tandon ◽  
Alberto Quaglia ◽  
Brian Davidson ◽  
...  
Keyword(s):  
Immune System ◽  
Calcium Release ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Calcium Influx ◽  
Calcium Signalling ◽  
Chronic Fatigue ◽  
Diverse Range ◽  
Immune System Activation

AbstractCalcium is the most abundant mineral in the human body and is central to many physiological processes, including immune system activation and maintenance. Studies continue to reveal the intricacies of calcium signalling within the immune system. Perhaps the most well-understood mechanism of calcium influx into cells is store-operated calcium entry (SOCE), which occurs via calcium release-activated channels (CRACs). SOCE is central to the activation of immune system cells; however, more recent studies have demonstrated the crucial role of other calcium channels, including transient receptor potential (TRP) channels. In this review, we describe the expression and function of TRP channels within the immune system and outline associations with murine models of disease and human conditions. Therefore, highlighting the importance of TRP channels in disease and reviewing potential. The TRP channel family is significant, and its members have a continually growing number of cellular processes. Within the immune system, TRP channels are involved in a diverse range of functions including T and B cell receptor signalling and activation, antigen presentation by dendritic cells, neutrophil and macrophage bactericidal activity, and mast cell degranulation. Not surprisingly, these channels have been linked to many pathological conditions such as inflammatory bowel disease, chronic fatigue syndrome and myalgic encephalomyelitis, atherosclerosis, hypertension and atopy.

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