scholarly journals Uncovering Novel Peptide Chemistry from Bacterial Natural Products

2021 ◽  
Vol 75 (6) ◽  
pp. 543-547
Author(s):  
Florian Hubrich ◽  
Alessandro Lotti ◽  
Thomas A. Scott ◽  
Jörn Piel
Keyword(s):  
Natural Products ◽  
Bioactive Peptides ◽  
Biological Activities ◽  
Biological Properties ◽  
Post Translational Modifications ◽  
Peptide Chemistry ◽  
Chemical Structures ◽  
Therapeutic Value ◽  
Modified Peptides ◽  
Unique Chemical

Nature has evolved a remarkable array of biosynthetic enzymes that install diverse chemistries into natural products (NPs), bestowing them with a range of important biological properties that are of considerable therapeutic value. This is epitomized by the ribosomally synthesized and post-translationally modified peptides (RiPPs), a class of peptide natural products that undergo extensive post-translational modifications to produce structurally diverse bioactive peptides. In this review, we provide an overview of our research into the proteusin RiPP family, describing characterized members and the maturation enzymes responsible for their unique chemical structures and biological activities. The diverse enzymology identified in the first two proteusin pathways highlights the enormous potential of the RiPP class for new lead structures and novel pharmacophore-installing maturases as biocatalytic tools for drug discovery efforts.

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.

scholarly journals New Scabimycins A-C Isolated from Streptomyces acidiscabies (Lu19992)

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5922
Author(s):  
Constanze Paulus ◽  
Josef Zapp ◽  
Andriy Luzhetskyy
Keyword(s):  
Natural Products ◽  
Bioactive Peptides ◽  
Biological Activities ◽  
Powerful Source ◽  
Drug Candidates ◽  
Chemical Structures ◽  
Wide Range ◽  
Streptomyces Acidiscabies ◽  
New Compounds ◽  
Important Drug

Peptide natural products displaying a wide range of biological activities have become important drug candidates over the years. Microorganisms have been a powerful source of such bioactive peptides, and Streptomyces have yielded many novel natural products thus far. In an effort to uncover such new, meaningful compounds, the metabolome of Streptomyces acidiscabies was analyzed thoroughly. Three new compounds, scabimycins A–C (1–3), were discovered, and their chemical structures were elucidated by NMR spectroscopy. The relative and absolute configurations were determined using ROESY NMR experiments and advanced Marfey’s method.

scholarly journals Current Advancements in Sactipeptide Natural Products

2021 ◽  
Vol 9 ◽  
Author(s):  
Yunliang Chen ◽  
Jinxiu Wang ◽  
Guoquan Li ◽  
Yunpeng Yang ◽  
Wei Ding
Keyword(s):  
Natural Products ◽  
Biological Activities ◽  
Cysteine Residue ◽  
Leader Peptide ◽  
Sequencing Technology ◽  
Chemical Structures ◽  
Precursor Peptide ◽  
Modified Peptides ◽  
Core Peptide ◽  
Alpha Carbon

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a growing class of natural products that benefited from genome sequencing technology in the past two decades. RiPPs are widely distributed in nature and show diverse chemical structures and rich biological activities. Despite the various structural characteristic of RiPPs, they follow a common biosynthetic logic: a precursor peptide containing an N-terminal leader peptide and a C-terminal core peptide; in some cases,a follower peptide is after the core peptide. The precursor peptide undergoes a series of modification, transport, and cleavage steps to form a mature natural product with specific activities. Sactipeptides (Sulfur-to-alpha carbon thioether cross-linked peptides) belong to RiPPs that show various biological activities such as antibacterial, spermicidal and hemolytic properties. Their common hallmark is an intramolecular thioether bond that crosslinks the sulfur atom of a cysteine residue to the α-carbon of an acceptor amino acid, which is catalyzed by a rSAM enzyme. This review summarizes recent achievements concerning the discovery, distribution, structural elucidation, biosynthesis and application prospects of sactipeptides.

scholarly journals DeepRiPP integrates multiomics data to automate discovery of novel ribosomally synthesized natural products

2019 ◽  
Vol 117 (1) ◽  
pp. 371-380 ◽  
Author(s):  
Nishanth J. Merwin ◽  
Walaa K. Mousa ◽  
Chris A. Dejong ◽  
Michael A. Skinnider ◽  
Michael J. Cannon ◽  
...  
Keyword(s):  
Machine Learning ◽  
Natural Products ◽  
Large Scale ◽  
Biological Activities ◽  
Learning Technologies ◽  
Genomic Context ◽  
Chemical Structures ◽  
Metabolomic Data ◽  
Comparative Metabolomics ◽  
Modified Peptides

Microbial natural products represent a rich resource of evolved chemistry that forms the basis for the majority of pharmacotherapeutics. Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a particularly interesting class of natural products noted for their unique mode of biosynthesis and biological activities. Analyses of sequenced microbial genomes have revealed an enormous number of biosynthetic loci encoding RiPPs but whose products remain cryptic. In parallel, analyses of bacterial metabolomes typically assign chemical structures to only a minority of detected metabolites. Aligning these 2 disparate sources of data could provide a comprehensive strategy for natural product discovery. Here we present DeepRiPP, an integrated genomic and metabolomic platform that employs machine learning to automate the selective discovery and isolation of novel RiPPs. DeepRiPP includes 3 modules. The first, NLPPrecursor, identifies RiPPs independent of genomic context and neighboring biosynthetic genes. The second module, BARLEY, prioritizes loci that encode novel compounds, while the third, CLAMS, automates the isolation of their corresponding products from complex bacterial extracts. DeepRiPP pinpoints target metabolites using large-scale comparative metabolomics analysis across a database of 10,498 extracts generated from 463 strains. We apply the DeepRiPP platform to expand the landscape of novel RiPPs encoded within sequenced genomes and to discover 3 novel RiPPs, whose structures are exactly as predicted by our platform. By building on advances in machine learning technologies, DeepRiPP integrates genomic and metabolomic data to guide the isolation of novel RiPPs in an automated manner.

Chitosan in Biomedical Engineering: A Critical Review

2019 ◽  
Vol 14 (2) ◽  
pp. 93-116 ◽  
Author(s):  
Shabnam Mohebbi ◽  
Mojtaba Nasiri Nezhad ◽  
Payam Zarrintaj ◽  
Seyed Hassan Jafari ◽  
Saman Seyed Gholizadeh ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Biomedical Engineering ◽  
Biological Properties ◽  
Advanced Materials ◽  
Comprehensive Overview ◽  
Chemical Structures ◽  
Bio Imaging ◽  
Significant Attention ◽  
Unique Chemical

Biomedical engineering seeks to enhance the quality of life by developing advanced materials and technologies. Chitosan-based biomaterials have attracted significant attention because of having unique chemical structures with desired biocompatibility and biodegradability, which play different roles in membranes, sponges and scaffolds, along with promising biological properties such as biocompatibility, biodegradability and non-toxicity. Therefore, chitosan derivatives have been widely used in a vast variety of uses, chiefly pharmaceuticals and biomedical engineering. It is attempted here to draw a comprehensive overview of chitosan emerging applications in medicine, tissue engineering, drug delivery, gene therapy, cancer therapy, ophthalmology, dentistry, bio-imaging, bio-sensing and diagnosis. The use of Stem Cells (SCs) has given an interesting feature to the use of chitosan so that regenerative medicine and therapeutic methods have benefited from chitosan-based platforms. Plenty of the most recent discussions with stimulating ideas in this field are covered that could hopefully serve as hints for more developed works in biomedical engineering.

Hemoglobin F (HbF) inducers; History, Structure and Efficacies

2021 ◽  
Vol 21 ◽  
Author(s):  
Zahra Hashemi ◽  
Mohammad Ali Ebrahimzadeh
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Biological Activities ◽  
Globin Gene ◽  
Beta Thalassemia ◽  
Gene Promoters ◽  
Hemoglobin F ◽  
Chemical Structures

Abstract: Inherited beta-thalassemia is a major disease caused by irregular production of hemoglobin through reducing beta-globin chains. It has been observed that increasing fetal hemoglobin (HbF) production improves symptoms in the patients. Therefore, an increase in the level of HbF has been an operative approach for treating patients with beta-thalassemia. This review represents compounds with biological activities and pharmacological properties that can promote the HBF level and therefore used in the β-thalassemia patients' therapy. Various natural products with different mechanisms of action can be helpful in this medication cure. Clinical trials were efficient in improving the signs of patients. Association of in vivo, and in vitro studies of HbF induction and γ-globin mRNA growth displays that in vitro experiments could be an indicator of the in vivo response. The current study shows that; (a) HbF inducers can be grouped in several classes based on their chemical structures and mechanism of actions; b) According to several clinical trials, well-known drugs such as hydroxyurea and decitabine are useful HbF inducers; (c) The cellular biosensor K562 carrying genes under the control of the human γ-globin and β-globin gene promoters were applied during the researches; d) New natural products and lead compounds were found based on various studies as HbF inducers.

The uniqueness and therapeutic value of natural products from West African medicinal plants, part III: least abundant compound classes

RSC Advances ◽  
2014 ◽  
Vol 4 (75) ◽  
pp. 40095-40110 ◽  
Author(s):  
Conrad V. Simoben ◽  
Fidele Ntie-Kang ◽  
Lydia L. Lifongo ◽  
Smith B. Babiaka ◽  
Wolfgang Sippl ◽  
...  
Keyword(s):  
Natural Products ◽  
Medicinal Plants ◽  
Biological Activities ◽  
West African ◽  
Therapeutic Value

In this review, a continuation of our in-depth coverage of natural products derived from West African medicinal plants with diverse biological activities has been given.

The uniqueness and therapeutic value of natural products from West African medicinal plants, part II: terpenoids, geographical distribution and drug discovery

RSC Advances ◽  
2014 ◽  
Vol 4 (67) ◽  
pp. 35348-35370 ◽  
Author(s):  
Fidele Ntie-Kang ◽  
Lydia L. Lifongo ◽  
Conrad V. Simoben ◽  
Smith B. Babiaka ◽  
Wolfgang Sippl ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Medicinal Plants ◽  
Geographical Distribution ◽  
Biological Activities ◽  
West African ◽  
Therapeutic Value

In this review series, an attempt has been made to give indepth coverage of natural products derived from West African medicinal plants with diverse biological activities.

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 Natural Indole Alkaloids from Marine Fungi: Chemical Diversity and Biological Activities

2021 ◽  
Author(s):  
Jiao Li ◽  
Chun-Lin Zhuang
Keyword(s):  
Marine Fungi ◽  
Biological Activities ◽  
Indole Alkaloids ◽  
Structural Diversity ◽  
Heterocyclic Ring ◽  
Chemical Diversity ◽  
Pharmaceutical Development ◽  
Chemical Structures ◽  
Clinical Drugs ◽  
Unique Chemical

The indole scaffold is one of the most important heterocyclic ring systems for pharmaceutical development, and serves as an active moiety in several clinical drugs. Fungi derived from marine origin are more liable to produce novel indole-containing natural products due to their extreme living environments. The indole alkaloids from marine fungi have drawn considerable attention for their unique chemical structures and significant biological activities. This review attempts to provide a summary of the structural diversity of marine fungal indole alkaloids including prenylated indoles, diketopiperazine indoles, bisindoles or trisindoles, quinazoline-containing indoles, indole-diterpenoids, and other indoles, as well as their known biological activities, mainly focusing on cytotoxic, kinase inhibitory, antiinflammatory, antimicrobial, anti-insecticidal, and brine shrimp lethal effects. A total of 306 indole alkaloids from marine fungi have been summarized, covering the references published from 1995 to early 2021, expecting to be beneficial for drug discovery in the future.

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