scholarly journals Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

2016 ◽  
Vol 12 ◽  
pp. 1250-1268 ◽  
Author(s):  
Andrew W Truman
Keyword(s):  
Amino Acids ◽  
Chemical Reactions ◽  
Chemical Space ◽  
Biological Activities ◽  
Chemical Diversity ◽  
Future Prospects ◽  
Signalling Molecules ◽  
Modified Peptides ◽  
Pathway Discovery ◽  
Anti Hiv

Ribosomally synthesised and post-translationally modified peptides (RiPPs) are a large class of natural products that are remarkably chemically diverse given an intrinsic requirement to be assembled from proteinogenic amino acids. The vast chemical space occupied by RiPPs means that they possess a wide variety of biological activities, and the class includes antibiotics, co-factors, signalling molecules, anticancer and anti-HIV compounds, and toxins. A considerable amount of RiPP chemical diversity is generated from cyclisation reactions, and the current mechanistic understanding of these reactions will be discussed here. These cyclisations involve a diverse array of chemical reactions, including 1,4-nucleophilic additions, [4 + 2] cycloadditions, ATP-dependent heterocyclisation to form thiazolines or oxazolines, and radical-mediated reactions between unactivated carbons. Future prospects for RiPP pathway discovery and characterisation will also be highlighted.

scholarly journals Chemical Diversity and Bioactivities of Monoterpene Indole Alkaloids (MIAs) from Six Apocynaceae Genera

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 488
Author(s):  
Afrah E. Mohammed ◽  
Zainab H. Abdul-Hameed ◽  
Modhi O. Alotaibi ◽  
Nahed O. Bawakid ◽  
Tariq R. Sobahi ◽  
...  
Keyword(s):  
Biological Activities ◽  
Indole Alkaloids ◽  
Natural Compounds ◽  
Molecular Target ◽  
Chemical Diversity ◽  
Drug Lead ◽  
The Family ◽  
Monoterpene Indole Alkaloids ◽  
Drug Leads ◽  
Anti Hiv

By the end of the twentieth century, the interest in natural compounds as probable sources of drugs has declined and was replaced by other strategies such as molecular target-based drug discovery. However, in the recent times, natural compounds regained their position as extremely important source drug leads. Indole-containing compounds are under clinical use which includes vinblastine and vincristine (anticancer), atevirdine (anti-HIV), yohimbine (erectile dysfunction), reserpine (antihypertension), ajmalicine (vascular disorders), ajmaline (anti-arrhythmic), vincamine (vasodilator), etc. Monoterpene Indole Alkaloids (MIAs) deserve the curiosity and attention of researchers due to their chemical diversity and biological activities. These compounds were considered as an impending source of drug-lead. In this review 444 compounds, were identified from six genera belonging to the family Apocynaceae, will be discussed. These genera (Alstonia, Rauvolfia, Kopsia, Ervatamia, and Tabernaemontana, and Rhazya) consist of 400 members and represent 20% of Apocynaceae species. Only 30 (7.5%) species were investigated, whereas the rest are promising to be investigated. Eleven bioactivities, including antibacterial, antifungal, anti-inflammatory and immunosuppressant activities, were reported. Whereas cytotoxic effect represents 47% of the reported activities. Convincingly, the genera selected in this review are a wealthy source for future anticancer drug lead.

scholarly journals Expanded Natural Product Diversity Revealed by Analysis of Lanthipeptide-Like Gene Clusters in Actinobacteria

2015 ◽  
Vol 81 (13) ◽  
pp. 4339-4350 ◽  
Author(s):  
Qi Zhang ◽  
James R. Doroghazi ◽  
Xiling Zhao ◽  
Mark C. Walker ◽  
Wilfred A. van der Donk
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Gene Cluster ◽  
Posttranslational Modifications ◽  
Large Scale ◽  
Biological Activities ◽  
Gene Clusters ◽  
Chemical Diversity ◽  
Content Type ◽  
Modified Peptides

ABSTRACTLanthionine-containing peptides (lanthipeptides) are a rapidly growing family of polycyclic peptide natural products belonging to the large class of ribosomally synthesized and posttranslationally modified peptides (RiPPs). Lanthipeptides are widely distributed in taxonomically distant species, and their currently known biosynthetic systems and biological activities are diverse. Building on the recent natural product gene cluster family (GCF) project, we report here large-scale analysis of lanthipeptide-like biosynthetic gene clusters fromActinobacteria. Our analysis suggests that lanthipeptide biosynthetic pathways, and by extrapolation the natural products themselves, are much more diverse than currently appreciated and contain many different posttranslational modifications. Furthermore, lanthionine synthetases are much more diverse in sequence and domain topology than currently characterized systems, and they are used by the biosynthetic machineries for natural products other than lanthipeptides. The gene cluster families described here significantly expand the chemical diversity and biosynthetic repertoire of lanthionine-related natural products. Biosynthesis of these novel natural products likely involves unusual and unprecedented biochemistries, as illustrated by several examples discussed in this study. In addition, class IV lanthipeptide gene clusters are shown not to be silent, setting the stage to investigate their biological activities.

scholarly journals Lessons from Exploring Chemical Space and Chemical Diversity of Propolis Components

2020 ◽  
Vol 21 (14) ◽  
pp. 4988 ◽  
Author(s):  
Trong D. Tran ◽  
Steven M. Ogbourne ◽  
Peter R. Brooks ◽  
Norberto Sánchez-Cruz ◽  
José L. Medina-Franco ◽  
...  
Keyword(s):  
Honey Bee ◽  
Broad Spectrum ◽  
Chemical Space ◽  
Biological Activities ◽  
Stingless Bee ◽  
Chemical Diversity ◽  
Commercial Interest ◽  
Compound Database ◽  
Ancient Times ◽  
Unique Compound

Propolis is a natural resinous material produced by bees and has been used in folk medicines since ancient times. Due to it possessing a broad spectrum of biological activities, it has gained significant scientific and commercial interest over the last two decades. As a result of searching 122 publications reported up to the end of 2019, we assembled a unique compound database consisting of 578 components isolated from both honey bee propolis and stingless bee propolis, and analyzed the chemical space and chemical diversity of these compounds. The results demonstrated that both honey bee propolis and stingless bee propolis are valuable sources for pharmaceutical and nutraceutical development.

scholarly journals Genomic charting of ribosomally synthesized natural product chemical space facilitates targeted mining

2016 ◽  
Vol 113 (42) ◽  
pp. E6343-E6351 ◽  
Author(s):  
Michael A. Skinnider ◽  
Chad W. Johnston ◽  
Robyn E. Edgar ◽  
Chris A. Dejong ◽  
Nishanth J. Merwin ◽  
...  
Keyword(s):  
Natural Products ◽  
Genome Sequencing ◽  
Sequence Data ◽  
Chemical Space ◽  
Biological Activities ◽  
Global Analysis ◽  
Gene Clusters ◽  
Systematic Investigation ◽  
Chemical Structures ◽  
Modified Peptides

Microbial natural products are an evolved resource of bioactive small molecules, which form the foundation of many modern therapeutic regimes. Ribosomally synthesized and posttranslationally modified peptides (RiPPs) represent a class of natural products which have attracted extensive interest for their diverse chemical structures and potent biological activities. Genome sequencing has revealed that the vast majority of genetically encoded natural products remain unknown. Many bioinformatic resources have therefore been developed to predict the chemical structures of natural products, particularly nonribosomal peptides and polyketides, from sequence data. However, the diversity and complexity of RiPPs have challenged systematic investigation of RiPP diversity, and consequently the vast majority of genetically encoded RiPPs remain chemical “dark matter.” Here, we introduce an algorithm to catalog RiPP biosynthetic gene clusters and chart genetically encoded RiPP chemical space. A global analysis of 65,421 prokaryotic genomes revealed 30,261 RiPP clusters, encoding 2,231 unique products. We further leverage the structure predictions generated by our algorithm to facilitate the genome-guided discovery of a molecule from a rare family of RiPPs. Our results provide the systematic investigation of RiPP genetic and chemical space, revealing the widespread distribution of RiPP biosynthesis throughout the prokaryotic tree of life, and provide a platform for the targeted discovery of RiPPs based on genome sequencing.

Chemical diversity and bioactivity of marine sponges of the genus Oceanapia: A review

2021 ◽  
Vol 18 ◽  
Author(s):  
Keisham S. Singh ◽  
Supriya Tilvi
Keyword(s):  
Secondary Metabolites ◽  
Pacific Coast ◽  
Biological Activities ◽  
Biological Properties ◽  
Marine Sponges ◽  
Chemical Diversity ◽  
Rich Source ◽  
Chemical Structures ◽  
Anti Hiv ◽  
Acetylenic Acids

: The marine sponges of the genus Oceanapia sp. is comprised of more than 50 species and are distributed in the seas around the tropical and subtropical regions. They are mainly found in the northern Indian oceans, Japan, and the south pacific coast. They are highly colored and known to be a rich source of various secondary metabolites, particularly, alkaloids. Several other secondary metabolites were also reported from this genus which include terpenes, sphingolipids, ceramides, cerebrosides, acetylenic acids, and thiocyanatins, etc. Many of these compounds isolated from this genus exhibited various biological properties including anticancer, antimicrobial, anti-HIV, ichthyotoxicity and nematocidal activities. Although several secondary metabolites have been reported from this genus, a dedicated review of the chemicals and biological activities of this genus is so far lacking. Keeping this in mind this review describes the various chemical entities isolated from the sponges of the genus Oceanapia detailing their chemical structures along with their reported biological properties.

scholarly journals Recombinant thiopeptides containing noncanonical amino acids

2016 ◽  
Vol 113 (13) ◽  
pp. 3615-3620 ◽  
Author(s):  
Xiaozhou Luo ◽  
Claudio Zambaldo ◽  
Tao Liu ◽  
Yuhan Zhang ◽  
Weimin Xuan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Chemical Reactivity ◽  
Biological Activities ◽  
Structural Diversity ◽  
Trna Synthetase ◽  
Aminoacyl Trna Synthetase ◽  
Noncanonical Amino Acids ◽  
Amber Suppressor ◽  
Modified Peptides ◽  
Biophysical Probes

Thiopeptides are a subclass of ribosomally synthesized and posttranslationally modified peptides (RiPPs) with complex molecular architectures and an array of biological activities, including potent antimicrobial activity. Here we report the generation of thiopeptides containing noncanonical amino acids (ncAAs) by introducing orthogonal amber suppressor aminoacyl-tRNA synthetase/tRNA pairs into a thiocillin producer strain ofBacillus cereus. We demonstrate that thiopeptide variants containing ncAAs with bioorthogonal chemical reactivity can be further postbiosynthetically modified with biophysical probes, including fluorophores and photo-cross-linkers. This work allows the site-specific incorporation of ncAAs into thiopeptides to increase their structural diversity and probe their biological activity; similar approaches can likely be applied to other classes of RiPPs.

scholarly journals Digitizing mass spectrometry data to explore the chemical diversity and distribution of marine cyanobacteria and algae

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Tal Luzzatto-Knaan ◽  
Neha Garg ◽  
Mingxun Wang ◽  
Evgenia Glukhov ◽  
Yao Peng ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Chemical Space ◽  
Biological Activities ◽  
Chemical Diversity ◽  
Mass Spectrometry Data ◽  
Marine Cyanobacteria ◽  
Dispersal Patterns ◽  
Screening Programs ◽  
Cyclic Lipopeptide ◽  
Cyanobacteria And Algae

Natural product screening programs have uncovered molecules from diverse natural sources with various biological activities and unique structures. However, much is yet underexplored and additional information is hidden in these exceptional collections. We applied untargeted mass spectrometry approaches to capture the chemical space and dispersal patterns of metabolites from an in-house library of marine cyanobacterial and algal collections. Remarkably, 86% of the metabolomics signals detected were not found in other available datasets of similar nature, supporting the hypothesis that marine cyanobacteria and algae possess distinctive metabolomes. The data were plotted onto a world map representing eight major sampling sites, and revealed potential geographic locations with high chemical diversity. We demonstrate the use of these inventories as a tool to explore the diversity and distribution of natural products. Finally, we utilized this tool to guide the isolation of a new cyclic lipopeptide, yuvalamide A, from a marine cyanobacterium.

scholarly journals Exploring the Chemical Space of Macro- and Micro-Algae Using Comparative Metabolomics

2021 ◽  
Vol 9 (2) ◽  
pp. 311
Author(s):  
Alison H. Hughes ◽  
Florent Magot ◽  
Ahmed F. Tawfike ◽  
Cecilia Rad-Menéndez ◽  
Naomi Thomas ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Biological Diversity ◽  
Chemical Space ◽  
Biological Activities ◽  
Chemical Diversity ◽  
Liquid Chromatography Mass Spectrometry ◽  
Depth Analysis ◽  
Comparative Metabolomics ◽  
Chemical Profiles

With more than 156,000 described species, eukaryotic algae (both macro- and micro-algae) are a rich source of biological diversity, however their chemical diversity remains largely unexplored. Specialised metabolites with promising biological activities have been widely reported for seaweeds, and more recently extracts from microalgae have exhibited activity in anticancer, antimicrobial, and antioxidant screens. However, we are still missing critical information on the distinction of chemical profiles between macro- and microalgae, as well as the chemical space these metabolites cover. This study has used an untargeted comparative metabolomics approach to explore the chemical diversity of seven seaweeds and 36 microalgal strains. A total of 1390 liquid chromatography-mass spectrometry (LC-MS) features were detected, representing small organic algal metabolites, with no overlap between the seaweeds and microalgae. An in-depth analysis of four Dunaliella tertiolecta strains shows that environmental factors may play a larger role than phylogeny when classifying their metabolomic profiles.

Tetrazoloquinolines: Synthesis, Reactions, and Applications

2020 ◽  
Vol 24 (4) ◽  
pp. 439-464 ◽  
Author(s):  
Rizk E. Khidre ◽  
Tahah A. Ameen ◽  
Mounir A. I. Salem
Keyword(s):  
Carboxylic Acid ◽  
Chemical Reactions ◽  
Sodium Azide ◽  
Biological Activities ◽  
Quinoline Derivatives ◽  
Pharmacological Activities ◽  
Synthesis Reactions ◽  
Intramolecular Cyclocondensation

This review summarizes the synthesis, reactions, and biological activities of tetrazolo[1,5-a]quinoline derivatives. These derivatives were synthesized by several methods such as i) from the reaction of 2-chloroquinoline with sodium azide ii) from diazotization 2-hydrazinylquinoline derivatives, and iii) from intramolecular cyclocondensation of 2-azidoarylidenes. Also, the chemical reactions and pharmacological activities of some tetrazoloquinolines such as tetrazolo[1,5-a]quinoline-4-carbaldehyde, 5-chlorotetrazolo[ 1,5-a]quinoline, 4-(chloromethyl)tetrazolo[1,5-a]quinoline, tetrazolo[1,5- a]quinoline-4-carboxylic acid, and 5-azidotetrazolo[1,5-a]quinoline were discussed.

Synthesis and Biological Activity of Quaternary Quinolinium Salts: A Review

2020 ◽  
Vol 23 (21) ◽  
pp. 2271-2294 ◽  
Author(s):  
Divya Utreja ◽  
Shivali Sharma ◽  
Akhil Goyal ◽  
Komalpreet Kaur ◽  
Sonia Kaushal
Keyword(s):  
Tyrosine Kinases ◽  
Biological Activities ◽  
Polymeric Materials ◽  
Tubulin Polymerization ◽  
Quinoline Derivatives ◽  
Heterocyclic Chemistry ◽  
Biological Profile ◽  
Drug Candidates ◽  
Anti Hiv ◽  
Quinolinium Salts

Heterocyclic chemistry is the only branch of chemistry that has applications in varied areas such as dyes, photosensitizers, coordination compounds, polymeric materials, biological, and many other fields. Quinoline and its derivatives have always engrossed both synthetic chemists and biologists because of their diverse chemical and pharmacological properties as these ring systems can be easily found in various natural products, especially in alkaloids. Among alkaloids, quinoline derivatives i.e. quinolinium salts have attracted much attention nowadays owing to their diverse biological profile such as antimicrobial, antitumor, antifungal, hypotensive, anti-HIV, analgesics and anti-inflammatory, etc. Quinoline and its analogs have recently been examined for their modes of function in the inhibition of tyrosine kinases, proteasome, tubulin polymerization, topoisomerase, and DNA repair. These observations have been guiding scientists for the expansion of new quinoline derivatives with improved and varied biological activities. Quinolinium salts have immense possibilities and scope to investigate these compounds as potential drug candidates. Therefore, we shall present a concise compilation of this work to aid in present knowledge and to help researchers explore an interesting quinoline class having medicinal potential.

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