scholarly journals Towards the production of tikitericin: A novel peptide from Thermogemmatispora strain T81

2021 ◽  
Author(s):  
◽  
Benjamin Baker
Keyword(s):  
Antimicrobial Activity ◽  
Natural Products ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Genome Mining ◽  
New Drugs ◽  
Taupo Volcanic Zone ◽  
Ms Imaging ◽  
Modified Peptides ◽  
Microbial Natural Products

<p>The utilisation of natural products for treatment of human ailments has been rooted in various cultures for centuries. Extraction of natural products has been essential for the discovery of new drugs and inspiration for synthetic analogues. Since the success of penicillin, microbial natural products have been of interest. Genome mining of Thermogemmatisporastrain T81, a thermophile from the Taupo Volcanic Zone, found the potential for the production of novel ribosomally synthesised and post-translationally modified peptides (RiPPs). Previous work showed that T81 exhibited antimicrobial activity against a wide variety of extremophillic bacteria. Although the three thiopeptides encoded forin the genome of T81 have not been found, the lanthipeptide tikitericin has recently been isolated and described. Unfortunately tikitericin is produced in low quantities by T81 andbioactivity data has not yet been obtained. Because of its potential antimicrobial activity, different routes to produce it are of interest. The aim of this project wasto synthesisetikitericin by solid phase peptide synthesis. MS imaging was also utilised to search for the presence of tikitericin as an antimicrobial agent in situ.</p>

scholarly journals Towards the production of tikitericin: A novel peptide from Thermogemmatispora strain T81

2021 ◽  
Author(s):  
◽  
Benjamin Baker
Keyword(s):  
Antimicrobial Activity ◽  
Natural Products ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Genome Mining ◽  
New Drugs ◽  
Taupo Volcanic Zone ◽  
Ms Imaging ◽  
Modified Peptides ◽  
Microbial Natural Products

<p>The utilisation of natural products for treatment of human ailments has been rooted in various cultures for centuries. Extraction of natural products has been essential for the discovery of new drugs and inspiration for synthetic analogues. Since the success of penicillin, microbial natural products have been of interest. Genome mining of Thermogemmatisporastrain T81, a thermophile from the Taupo Volcanic Zone, found the potential for the production of novel ribosomally synthesised and post-translationally modified peptides (RiPPs). Previous work showed that T81 exhibited antimicrobial activity against a wide variety of extremophillic bacteria. Although the three thiopeptides encoded forin the genome of T81 have not been found, the lanthipeptide tikitericin has recently been isolated and described. Unfortunately tikitericin is produced in low quantities by T81 andbioactivity data has not yet been obtained. Because of its potential antimicrobial activity, different routes to produce it are of interest. The aim of this project wasto synthesisetikitericin by solid phase peptide synthesis. MS imaging was also utilised to search for the presence of tikitericin as an antimicrobial agent in situ.</p>

scholarly journals Recent Advances in Discovery of Lead Structures from Microbial Natural Products: Genomics- and Metabolomics-Guided Acceleration

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2542
Author(s):  
Linda Sukmarini
Keyword(s):  
Natural Products ◽  
Genome Mining ◽  
Screening Methods ◽  
Technological Advancement ◽  
Natural Origin ◽  
Drug Discovery And Development ◽  
New Methodologies ◽  
Analytical Instrumentation ◽  
Microbial Natural Products ◽  
Drug Leads

Natural products (NPs) are evolutionarily optimized as drug-like molecules and remain the most consistently successful source of drugs and drug leads. They offer major opportunities for finding novel lead structures that are active against a broad spectrum of assay targets, particularly those from secondary metabolites of microbial origin. Due to traditional discovery approaches’ limitations relying on untargeted screening methods, there is a growing trend to employ unconventional secondary metabolomics techniques. Aided by the more in-depth understanding of different biosynthetic pathways and the technological advancement in analytical instrumentation, the development of new methodologies provides an alternative that can accelerate discoveries of new lead-structures of natural origin. This present mini-review briefly discusses selected examples regarding advancements in bioinformatics and genomics (focusing on genome mining and metagenomics approaches), as well as bioanalytics (mass-spectrometry) towards the microbial NPs-based drug discovery and development. The selected recent discoveries from 2015 to 2020 are featured herein.

scholarly journals Effects of Dimerization on the Structure and Biological Activity of Antimicrobial Peptide Ctx-Ha

2012 ◽  
Vol 56 (6) ◽  
pp. 3004-3010 ◽  
Author(s):  
E. N. Lorenzón ◽  
G. F. Cespedes ◽  
E. F. Vicente ◽  
L. G. Nogueira ◽  
T. M. Bauab ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Biological Activity ◽  
Antimicrobial Peptide ◽  
Hemolytic Activity ◽  
Pore Diameter ◽  
Solid Phase ◽  
Biological Activities ◽  
Solid Phase Peptide Synthesis ◽  
Activity Assay ◽  
Growth Of Bacteria

ABSTRACTIt is well known that cationic antimicrobial peptides (cAMPs) are potential microbicidal agents for the increasing problem of antimicrobial resistance. However, the physicochemical properties of each peptide need to be optimized for clinical use. To evaluate the effects of dimerization on the structure and biological activity of the antimicrobial peptide Ctx-Ha, we have synthesized the monomeric and three dimeric (Lys-branched) forms of the Ctx-Ha peptide by solid-phase peptide synthesis using a combination of 9-fluorenylmethyloxycarbonyl (Fmoc) andt-butoxycarbonyl (Boc) chemical approaches. The antimicrobial activity assay showed that dimerization decreases the ability of the peptide to inhibit growth of bacteria or fungi; however, the dimeric analogs displayed a higher level of bactericidal activity. In addition, a dramatic increase (50 times) in hemolytic activity was achieved with these analogs. Permeabilization studies showed that the rate of carboxyfluorescein release was higher for the dimeric peptides than for the monomeric peptide, especially in vesicles that contained sphingomyelin. Despite different biological activities, the secondary structure and pore diameter were not significantly altered by dimerization. In contrast to the case for other dimeric cAMPs, we have shown that dimerization selectively decreases the antimicrobial activity of this peptide and increases the hemolytic activity. The results also show that the interaction between dimeric peptides and the cell wall could be responsible for the decrease of the antimicrobial activity of these peptides.

scholarly journals Biosynthetic investigation of phomopsins reveals a widespread pathway for ribosomal natural products in Ascomycetes

2016 ◽  
Vol 113 (13) ◽  
pp. 3521-3526 ◽  
Author(s):  
Wei Ding ◽  
Wan-Qiu Liu ◽  
Youli Jia ◽  
Yongzhen Li ◽  
Wilfred A. van der Donk ◽  
...  
Keyword(s):  
Natural Products ◽  
Biological Activities ◽  
Genome Mining ◽  
Substrate Specificities ◽  
Modified Peptides ◽  
Fungal Natural Products ◽  
Different Strains

Production of ribosomally synthesized and posttranslationally modified peptides (RiPPs) has rarely been reported in fungi, even though organisms of this kingdom have a long history as a prolific source of natural products. Here we report an investigation of the phomopsins, antimitotic mycotoxins. We show that phomopsin is a fungal RiPP and demonstrate the widespread presence of a pathway for the biosynthesis of a family of fungal cyclic RiPPs, which we term dikaritins. We characterize PhomM as an S-adenosylmethionine–dependent α-N-methyltransferase that converts phomopsin A to anN,N-dimethylated congener (phomopsin E), and show that the methyltransferases involved in dikaritin biosynthesis have evolved differently and likely have broad substrate specificities. Genome mining studies identified eight previously unknown dikaritins in different strains, highlighting the untapped capacity of RiPP biosynthesis in fungi and setting the stage for investigating the biological activities and unknown biosynthetic transformations of this family of fungal natural products.

scholarly journals Solid-phase enrichment and analysis of electrophilic natural products

2017 ◽  
Vol 13 ◽  
pp. 405-409 ◽  
Author(s):  
Frank Wesche ◽  
Yue He ◽  
Helge B Bode
Keyword(s):  
Natural Products ◽  
Solid Phase ◽  
New Drugs ◽  
Crude Extracts ◽  
Novel Methods

In search for new natural products, which may lead to the development of new drugs for all kind of applications, novel methods are needed. Here we describe the identification of electrophilic natural products in crude extracts via their reactivity against azide as a nucleophile followed by their subsequent enrichment using a cleavable azide-reactive resin (CARR). Using this approach, natural products carrying epoxides and α,β-unsaturated enones as well as several unknown compounds were identified in crude extracts from entomopathogenic Photorhabdus bacteria.

Synthesis of Side-Chain Modified Peptides Using Iterative Solid Phase ‘Click' Methodology

2017 ◽  
Vol 70 (2) ◽  
pp. 201 ◽  
Author(s):  
Xuejian Liu ◽  
Robert B. P. Elmes ◽  
Katrina A. Jolliffe
Keyword(s):  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Anion Recognition ◽  
Iterative Sequence ◽  
Side Chain ◽  
Short Peptides ◽  
Click Reactions ◽  
Fluorescent Indicators ◽  
Modified Peptides ◽  
Recognition Motifs

A series of side-chain modified peptides have been prepared via an iterative sequence of peptide couplings and azide–alkyne cycloadditions (‘click’ reactions) using Fmoc-solid phase peptide synthesis. This efficient modular synthetic route allows the systematic and sequential incorporation of a variety of side-chain modifications onto short peptides. The versatility of this approach was demonstrated by the synthesis of a series of short peptides with appended anion recognition motifs and fluorescent indicators.

scholarly journals A Multi-Omics Characterization of the Natural Product Potential of Tropical Filamentous Marine Cyanobacteria

Marine Drugs ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 20
Author(s):  
Tiago Leão ◽  
Mingxun Wang ◽  
Nathan Moss ◽  
Ricardo da Silva ◽  
Jon Sanders ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Genome Mining ◽  
Gene Clusters ◽  
Microbial Interactions ◽  
Marine Cyanobacteria ◽  
Pharmaceutical Drugs ◽  
Genes Encoding ◽  
Microbial Natural Products

Microbial natural products are important for the understanding of microbial interactions, chemical defense and communication, and have also served as an inspirational source for numerous pharmaceutical drugs. Tropical marine cyanobacteria have been highlighted as a great source of new natural products, however, few reports have appeared wherein a multi-omics approach has been used to study their natural products potential (i.e., reports are often focused on an individual natural product and its biosynthesis). This study focuses on describing the natural product genetic potential as well as the expressed natural product molecules in benthic tropical cyanobacteria. We collected from several sites around the world and sequenced the genomes of 24 tropical filamentous marine cyanobacteria. The informatics program antiSMASH was used to annotate the major classes of gene clusters. BiG-SCAPE phylum-wide analysis revealed the most promising strains for natural product discovery among these cyanobacteria. LCMS/MS-based metabolomics highlighted the most abundant molecules and molecular classes among 10 of these marine cyanobacterial samples. We observed that despite many genes encoding for peptidic natural products, peptides were not as abundant as lipids and lipopeptides in the chemical extracts. Our results highlight a number of highly interesting biosynthetic gene clusters for genome mining among these cyanobacterial samples.

scholarly journals Synthesis and Biological Studies on (KLAKLAK)2-NH2 Analog Containing Unnatural Amino Acid β-Ala and Conjugates with Second Pharmacophore

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7321
Author(s):  
Sirine Jaber ◽  
Veronica Nemska ◽  
Ivan Iliev ◽  
Elena Ivanova ◽  
Tsvetelina Foteva ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Solid Phase ◽  
Hydrolytic Stability ◽  
Solid Phase Peptide Synthesis ◽  
Unnatural Amino Acid ◽  
The Body ◽  
Diffusion Method ◽  
Anticancer Properties ◽  
Biological Studies

(1) Background: Peptides are good candidates for anticancer drugs due to their natural existence in the body and lack of secondary effects. (KLAKLAK)2 is an antimicrobial peptide that also shows good anticancer properties. (2) Methods: The Solid Phase Peptide Synthesis (Fmoc-strategy) was used for the synthesis of target molecules, analogs of (KLAKLAK)2-NH2. The purity of all compounds was monitored by HPLC, and their structures were proven using mass spectrometry. Cytotoxicity and antiproliferative effects were studied using 3T3 NRU and MTT tests, respectively. For determination of antimicrobial activity, the disc-diffusion method was used. Hydrolytic stability at three pH values, which mimic the physiological pH in the body, was investigated by means of the HPLC technique. (3) Results: A good selective index against MCF-7 tumor cell lines, combined with good cytotoxicity and antiproliferative properties, was revealed for conjugates NphtG-(KLAKLAK)2-NH2 and Caf-(KLAKLAK)2-NH2. The same compounds showed very good antifungal properties and complete hydrolytic stability for 72 h. The compound Caf-(KLβ-AKLβ-AK)2-NH2 containing β-Ala in its structures exhibited good antimicrobial activity against Escherichia coli K12 407 and Bacillus subtilis 3562, in combination with very good antiproliferative and cytotoxic properties, as well as hydrolytic stability. (4) Conclusions: The obtained results reveal that all synthesized conjugates could be useful for medical practice as anticancer or antimicrobial agents.

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