scholarly journals Diversity of Monomers in Nonribosomal Peptides: towards the Prediction of Origin and Biological Activity

2010 ◽  
Vol 192 (19) ◽  
pp. 5143-5150 ◽  
Author(s):  
Ségolène Caboche ◽  
Valérie Leclère ◽  
Maude Pupin ◽  
Gregory Kucherov ◽  
Philippe Jacques

ABSTRACT Nonribosomal peptides (NRPs) are molecules produced by microorganisms that have a broad spectrum of biological activities and pharmaceutical applications (e.g., antibiotic, immunomodulating, and antitumor activities). One particularity of the NRPs is the biodiversity of their monomers, extending far beyond the 20 proteogenic amino acid residues. Norine, a comprehensive database of NRPs, allowed us to review for the first time the main characteristics of the NRPs and especially their monomer biodiversity. Our analysis highlighted a significant similarity relationship between NRPs synthesized by bacteria and those isolated from metazoa, especially from sponges, supporting the hypothesis that some NRPs isolated from sponges are actually synthesized by symbiotic bacteria rather than by the sponges themselves. A comparison of peptide monomeric compositions as a function of biological activity showed that some monomers are specific to a class of activities. An analysis of the monomer compositions of peptide products predicted from genomic information (metagenomics and high-throughput genome sequencing) or of new peptides detected by mass spectrometry analysis applied to a culture supernatant can provide indications of the origin of a peptide and/or its biological activity.

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5916
Author(s):  
Željka Peršurić ◽  
Lara Saftić Martinović ◽  
Mladenka Malenica ◽  
Ivana Gobin ◽  
Sandra Pedisić ◽  
...  

Pomegranate (Punica granatum L.) is a rich source of constituents with confirmed strong biological activities. However, pomegranate peel, which encompasses approximately 30–40% of its weight, is treated as a biological waste. The aim of this paper was to evaluate the potential of pomegranate peel extracts and to propose its functional properties that can be used for development of functional products. Eight ethanol extracts of pomegranate peels (PPEs) were characterized by use of direct infusion quadrupole-time of flight (Q-TOF), and afterwards tested on their antioxidant, antibacterial and antiproliferative activities. Mass spectrometry analysis revealed that the most prevalent compounds in pomegranate peels were punicalagin, granatin and their derivatives. Analysed extracts had high total phenolic contents that ranged from 5766.44 to 10599.43 mg GAE/100 g, and strong antioxidant activity (7551.31–7875.42 and 100.25–176.60 μmol TE/100 g for DPPH and FRAP assays, respectively). The results of biological activity assays showed that all PPEs possessed antibacterial activity, and that S. aureus was the most sensitive specie with minimum inhibitory concentration and minimum bactericidal concentrations ranging from 0.8 to 6.4 mg/mL. Additionally, the analysis of antiproliferative activity revealed high potency of PPEs, as the IC50 values ranged from 0.132 mg/mL to 0.396 mg/mL. Multivariate analysis pointed out the most discriminative metabolites for antioxidant or antiproliferative activity. Overall, the pomegranate peel confirmed to be a highly valuable source of bioactive compounds that could be used to improve the food functional characteristics.


Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1804
Author(s):  
Izabela Perkowska ◽  
Joanna Siwinska ◽  
Alexandre Olry ◽  
Jérémy Grosjean ◽  
Alain Hehn ◽  
...  

Coumarins are phytochemicals occurring in the plant kingdom, which biosynthesis is induced under various stress factors. They belong to the wide class of specialized metabolites well known for their beneficial properties. Due to their high and wide biological activities, coumarins are important not only for the survival of plants in changing environmental conditions, but are of great importance in the pharmaceutical industry and are an active source for drug development. The identification of coumarins from natural sources has been reported for different plant species including a model plant Arabidopsis thaliana. In our previous work, we demonstrated a presence of naturally occurring intraspecies variation in the concentrations of scopoletin and its glycoside, scopolin, the major coumarins accumulating in Arabidopsis roots. Here, we expanded this work by examining a larger group of 28 Arabidopsis natural populations (called accessions) and by extracting and analysing coumarins from two different types of tissues–roots and leaves. In the current work, by quantifying the coumarin content in plant extracts with ultra-high-performance liquid chromatography coupled with a mass spectrometry analysis (UHPLC-MS), we detected a significant natural variation in the content of simple coumarins like scopoletin, umbelliferone and esculetin together with their glycosides: scopolin, skimmin and esculin, respectively. Increasing our knowledge of coumarin accumulation in Arabidopsis natural populations, might be beneficial for the future discovery of physiological mechanisms of action of various alleles involved in their biosynthesis. A better understanding of biosynthetic pathways of biologically active compounds is the prerequisite step in undertaking a metabolic engineering research.


2020 ◽  
Author(s):  
Bo Wei ◽  
Patrick Willems ◽  
Jingjing Huang ◽  
Caiping Tian ◽  
Jing Yang ◽  
...  

ABSTRACTIn proteins, hydrogen peroxide (H2O2) reacts with redox-sensitive cysteines to form cysteine sulfenic acid, also known as S-sulfenylation. These cysteine oxidation events can steer diverse cellular processes by altering protein interactions, trafficking, conformation, and function. Previously, we had identified S-sulfenylated proteins by using a tagged proteinaceous probe based on the yeast AP-1–like (Yap1) transcription factor that specifically reacts with sulfenic acids and traps them through a mixed disulfide bond. However, the identity of the S-sulfenylated amino acid residues remained enigmatic. Here, we present a technological advancement to identify in situ sulfenylated cysteines directly by means of the transgenic Yap1 probe. In Arabidopsis thaliana cells, after an initial affinity purification and a tryptic digestion, we further enriched the mixed disulfide-linked peptides with an antibody targeting the YAP1C-derived peptide (C598SEIWDR) that entails the redox-active cysteine. Subsequent mass spectrometry analysis with pLink 2 identified 1,745 YAP1C cross-linked peptides, indicating sulfenylated cysteines in over 1,000 proteins. Approximately 55% of these YAP1C-linked cysteines had previously been reported as redox-sensitive cysteines (S-sulfenylation, S-nitrosylation, and reversibly oxidized cysteines). The presented methodology provides a noninvasive approach to identify sulfenylated cysteines in any species that can be genetically modified.


2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Aitor Martinez ◽  
Juanma Ramirez ◽  
Nerea Osinalde ◽  
Jesus M. Arizmendi ◽  
Ugo Mayor

Both Parkin and UBE3A are E3 ubiquitin ligases whose mutations result in severe brain dysfunction. Several of their substrates have been identified using cell culture models in combination with proteasome inhibitors, but not in more physiological settings. We recently developed theUbbiostrategy to isolate ubiquitinated proteins in flies and have now identified by mass spectrometry analysis the neuronal proteins differentially ubiquitinated by those ligases. This is an example of how flies can be used to provide biological material in order to reveal steady state substrates of disease causing genes. Collectively our results provide new leads to the possible physiological functions of the activity of those two disease causing E3 ligases. Particularly, in the case of Parkin the novelty of our data originates from the experimental setup, which is not overtly biased by acute mitochondrial depolarisation. In the case of UBE3A, it is the first time that a nonbiased screen for its neuronal substrates has been reported.


Author(s):  
S. Navaith Ahmed ◽  
P. Kalaivani ◽  
P. Amudha ◽  
B. Usharani

Sea grass are good source of potent drug which has medicinal properties and able to cure human disease. One such marine plant is the Enhalus acoroides which belong to hydrocharitaeceae family. This marine species are widely distributed in the tropics of Indian and western Pacific Ocean and the species were collected from Ramanathapuram district for further process. This study reveals about the bioactive components present in Enhalus acoroides and identified its biological activity by Gas chromatography Mass spectrometry analysis using hydroalcoholic extract. The compounds present in Enhalus acoroides are Benzoic acid, 2- methyl 7- oxa bicyclol heptanes, 1, 3 Nonadiene, silane, ethoxytriethyl. Biological activities of the compounds present in the sample include antioxidant, hypocholesterolemic, antihypertensive, anti-inflammatory, anti-microbial, antiviral and anti-hepatotoxic effect.


Author(s):  
Kuladip Gurav ◽  
Varsha Jadhav (rathod)

Objective: The aim was to investigate important bioactive compounds, biological activities, and medicinal importance of Zanthoxylum rhetsa fruits.Methods: The present work was carried out by gas chromatography–mass spectrometry (GC-MS) method for the identification of different compounds.Result: The methanolic extract of fruits showed 32 chemical compounds which are identified through GC-MS analysis. Among them, some of the compound names and percentage values are as follows: 2-propanone, 1,3-dihydroxy (48.9%), 4H-pyran-4-one,2,3-dihydro-3,5-dihydroxy-6-methyl (33.7%), 2-furancarboxaldehyde, 5-[hydroxymethyl] (50.2%), 1-Heptatriacontanol (34.4%), 9,12-octadecadienoic acid (zz)- (48.6%), cholestan- 3-ol,2-methylene, [3β,5α] (75.0%), 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl (90.8), 2-furancarboxaldehyde, 5-[hydroxymethyl] (92.0%), hydroquinone (64.9%), n-hexadecanoic acid (37.5%), octadecanoic acid (28.2%), 9,12,15, octadecatrienoic acid, 2-[(trimethylsiyl]oxy]-1- [(trimethylsiyl]oxy]methyl] ethyl ester, [zzz] (22.6%), 9-hexadecanoic acid (10.3%), digitoxin (18.8%), 8,11,14-eicosatrienoic acid methyl ester, [zzz] (25.5%), and oleic acid (16.5%). Most of the identified compounds in the crude methanolic extracts exhibit some bioactivities, namely anticancer, anti-inflammatory, antimicrobial, hepatoprotective, antioxidant, hypocholesterolemic, nematicide, pesticide, anti-androgenic flavor, hemolytic, 5-alpha-reductase inhibitor, insectifuge, antiarthritic, anti-coronary, cardiovascular, anti-breast cancer, aromatic, and insectifuge. On the basis of the above investigation, the fruits can be recommended as a treasure of bioactive compounds and it plays a promising role in herbal medicine.Conclusion: The present study reveals that fruits of Z. rhetsa contain various bioactive compounds. Digitoxin is recorded in the ripened fruit of Z. rhetsa and it shows the anticancerous and cardiac arrest properties. Hence, in future, this plant will play a promising role in curing cancer.


Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3343 ◽  
Author(s):  
Seung-Yeap Song ◽  
Dae-Hun Park ◽  
Seong-Wook Seo ◽  
Kyung-Mok Park ◽  
Chun-Sik Bae ◽  
...  

Ginseng (Panax ginseng) has long been used as a traditional medicine for the prevention and treatment of various diseases. Generally, the harvest time and age of ginseng have been regarded as important factors determining the efficacy of ginseng. However, most studies have mainly focused on the root of ginseng, while studies on other parts of ginseng such as its berry have been relatively limited. Thus, the aim of this study iss to determine effects of harvest time on yields, phenolics/ginsenosides contents, and the antioxidant/anti-elastase activities of ethanol extracts of three- and four-year-old ginseng berry. In both three- and fourfour-year-old ginseng berry extracts, antioxidant and anti-elastase activities tended to increase as berries ripen from the first week to the last week of July. Liquid chromatography-tandem mass spectrometry analysis has revealed that contents of ginsenosides except Rg1 tend to be the highest in fourfour-year-old ginseng berries harvested in early July. These results indicate that biological activities and ginsenoside profiles of ginseng berry extracts depend on their age and harvest time in July, suggesting the importance of harvest time in the development of functional foods and medicinal products containing ginseng berry extracts. To the best of our knowledge, this is the first report on the influence of harvest time on the biological activity and ginsenoside contents of ginseng berry extracts.


Toxicon ◽  
2008 ◽  
Vol 51 (8) ◽  
pp. 1499-1508 ◽  
Author(s):  
Elisabeth F. Schwartz ◽  
Thalita S. Camargos ◽  
Fernando Z. Zamudio ◽  
Luciano P. Silva ◽  
Carlos Bloch ◽  
...  

2002 ◽  
Vol 184 (3) ◽  
pp. 629-635 ◽  
Author(s):  
J. M. Nieto ◽  
C. Madrid ◽  
E. Miquelay ◽  
J. L. Parra ◽  
S. Rodríguez ◽  
...  

ABSTRACT Escherichia coli nucleoid-associated H-NS protein interacts with the Hha protein, a member of a new family of global modulators that also includes the YmoA protein from Yersinia enterocolitica. This interaction has been found to be involved in the regulation of the expression of the toxin α-hemolysin. In this study, we further characterize the interaction between H-NS and Hha. We show that the presence of DNA in preparations of copurified His-Hha and H-NS is not directly implicated in the interaction between the proteins. The precise molecular mass of the H-NS protein retained by Hha, obtained by mass spectrometry analysis, does not show any posttranslational modification other than removal of the N-terminal Met residue. We constructed an H-NS-His recombinant protein and found that, as expected, it interacts with Hha. We used a Ni2+-nitrilotriacetic acid agarose method for affinity chromatography copurification of proteins to identify the H-NS protein of Y. enterocolitica. We constructed a six-His-YmoA recombinant protein derived from YmoA, the homologue of Hha in Y. enterocolitica, and found that it interacts with Y. enterocolitica H-NS. We also cloned and sequenced the hns gene of this microorganism. In the course of these experiments we found that His-YmoA can also retain H-NS from E. coli. We also found that the hns gene of Y. enterocolitica can complement an hns mutation of E. coli. Finally, we describe for the first time systematic characterization of missense mutant alleles of hha and truncated Hha′ proteins, and we report a striking and previously unnoticed similarity of the Hha family of proteins to the oligomerization domain of the H-NS proteins.


Author(s):  
Marie Bicikova ◽  
Martin Hill ◽  
Daniela Ripova ◽  
Pavel Mohr

AbstractThe role of GABAergic pathways in the pathophysiology of schizophrenia is generally accepted. Therefore, the information concerning alterations of the steroid metabolome associated with the disease and/or its treatment is of interest with regard to the pathophysiology of the disease. Hence, we assessed 18 serum steroids and steroid polar conjugates in a group of drug-naive patients (13 adult men) and after 6-months therapy by atypical antipsychotics and age-matched controls (19 men) using gas chromatography-mass spectrometry analysis. This study, for the first time, demonstrates the altered circulating GABAergic steroids in schizophrenic men as well as the effect of the therapy with two types of atypical antipsychotics. The GABAergic androsterone (3α5α) and etiocholanolone (3α5β) are reduced in schizophrenic men but the therapy with atypical antipsychotics reinstates their levels. This reinstatement could be of importance when considering that the GABAergic substances generally improve the well-being of patients. In addition to the unconjugated androsterone, being the most abundant GABAergic steroid in men, most of the other GABAergic steroids also tended to decrease in the patients. By contrast, the conjugated 5β-pregnanolone isomers were elevated in the patients. In conclusion, although schizophrenia status in adult men is associated with unfavorable alterations in neuroactive steroids, the treatment with antipsychotics could at least partly reinstate their circulating levels.


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