scholarly journals Control of Nucleophile Chemoselectivity in Cyanobactin YcaO Heterocyclases PatD and TruD

2021 ◽  
Author(s):  
Wenjia Gu ◽  
Yiwu Zheng ◽  
Taras Pogorelov ◽  
Satish K. Nair ◽  
Eric W. Schmidt
Keyword(s):  
Natural Products ◽  
Synthetic Biology ◽  
Post Translational Modifications ◽  
Pharmaceutical Development ◽  
The World ◽  
Academic Settings ◽  
Living Organisms

<div><div><div><p>YcaO proteins are ubiquitous in living organisms, where they perform crucial post-translational modifications of peptides and proteins. They are used extensively in biotechnology in companies and academic settings around the world. They also underlie some of the most important natural products in pharmaceutical development, such as thiopeptides (thiostrepton, etc.). Here, we solve one of the major outstanding mysteries behind YcaO proteins: how they exert precision selectivity of the nucleophile. The resulting findings have major implications in understanding the >30,000 YcaO proteins currently in sequencing databases and will be used widely for precision synthetic biology applications.</p></div></div></div>

scholarly journals Control of Nucleophile Chemoselectivity in Cyanobactin YcaO Heterocyclases PatD and TruD

2021 ◽  
Author(s):  
Wenjia Gu ◽  
Yiwu Zheng ◽  
Taras Pogorelov ◽  
Satish K. Nair ◽  
Eric W. Schmidt
Keyword(s):  
Natural Products ◽  
Synthetic Biology ◽  
Post Translational Modifications ◽  
Pharmaceutical Development ◽  
The World ◽  
Academic Settings ◽  
Living Organisms

<div><div><div><p>YcaO proteins are ubiquitous in living organisms, where they perform crucial post-translational modifications of peptides and proteins. They are used extensively in biotechnology in companies and academic settings around the world. They also underlie some of the most important natural products in pharmaceutical development, such as thiopeptides (thiostrepton, etc.). Here, we solve one of the major outstanding mysteries behind YcaO proteins: how they exert precision selectivity of the nucleophile. The resulting findings have major implications in understanding the >30,000 YcaO proteins currently in sequencing databases and will be used widely for precision synthetic biology applications.</p></div></div></div>

scholarly journals Biosynthesis and molecular engineering of templated natural products

2016 ◽  
Vol 4 (4) ◽  
pp. 553-575 ◽  
Author(s):  
Ming Chen ◽  
Jingyu Liu ◽  
Panpan Duan ◽  
Mulin Li ◽  
Wen Liu
Keyword(s):  
Natural Products ◽  
Critical Role ◽  
Structural Complexity ◽  
Limited Range ◽  
Molecular Engineering ◽  
First Century ◽  
Design Development ◽  
Post Translational Modifications ◽  
Development And Utilization ◽  
Living Organisms

Abstract Bioactive small molecules that are produced by living organisms, often referred to as natural products (NPs), historically play a critical role in the context of both medicinal chemistry and chemical biology. How nature creates these chemical entities with stunning structural complexity and diversity using a limited range of simple substrates has not been fully understood. Focusing on two types of NPs that share a highly evolvable ‘template’-biosynthetic logic, we here provide specific examples to highlight the conceptual and technological leaps in NP biosynthesis and witness the area of progress since the beginning of the twenty-first century. The biosynthesis of polyketides, non-ribosomal peptides and their hybrids that share an assembly-line enzymology of modular multifunctional proteins exemplifies an extended ‘central dogma’ that correlates the genotype of catalysts with the chemotype of products; in parallel, post-translational modifications of ribosomally synthesized peptides involve a number of unusual biochemical mechanisms for molecular maturation. Understanding the biosynthetic processes of these templated NPs would largely facilitate the design, development and utilization of compatible biosynthetic machineries to address the challenge that often arises from structural complexity to the accessibility and efficiency of current chemical synthesis.

scholarly journals COCONUT online: Collection of Open Natural Products database

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Maria Sorokina ◽  
Peter Merseburger ◽  
Kohulan Rajan ◽  
Mehmet Aziz Yirik ◽  
Christoph Steinbeck
Keyword(s):  
Natural Products ◽  
Small Molecules ◽  
In Silico ◽  
Web Interface ◽  
Computational Screening ◽  
Online Resource ◽  
The World ◽  
Potential Applications ◽  
Living Organisms ◽  
Application Fields

AbstractNatural products (NPs) are small molecules produced by living organisms with potential applications in pharmacology and other industries as many of them are bioactive. This potential raised great interest in NP research around the world and in different application fields, therefore, over the years a multiplication of generalistic and thematic NP databases has been observed. However, there is, at this moment, no online resource regrouping all known NPs in just one place, which would greatly simplify NPs research and allow computational screening and other in silico applications. In this manuscript we present the online version of the COlleCtion of Open Natural prodUcTs (COCONUT): an aggregated dataset of elucidated and predicted NPs collected from open sources and a web interface to browse, search and easily and quickly download NPs. COCONUT web is freely available at https://coconut.naturalproducts.net.

scholarly journals Genome Mining as New Challenge in Natural Products Discovery

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 199 ◽  
Author(s):  
Luisa Albarano ◽  
Roberta Esposito ◽  
Nadia Ruocco ◽  
Maria Costantini
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Synthetic Biology ◽  
Anticancer Agents ◽  
Genome Mining ◽  
Bioactive Natural Products ◽  
Advantages And Disadvantages ◽  
A Genome ◽  
Living Organisms ◽  
Natural Drugs

Drug discovery is based on bioactivity screening of natural sources, traditionally represented by bacteria fungi and plants. Bioactive natural products and their secondary metabolites have represented the main source for new therapeutic agents, used as drug leads for new antibiotics and anticancer agents. After the discovery of the first biosynthetic genes in the last decades, the researchers had in their hands the tool to understand the biosynthetic logic and genetic basis leading to the production of these compounds. Furthermore, in the genomic era, in which the number of available genomes is increasing, genome mining joined to synthetic biology are offering a significant help in drug discovery. In the present review we discuss the importance of genome mining and synthetic biology approaches to identify new natural products, also underlining considering the possible advantages and disadvantages of this technique. Moreover, we debate the associated techniques that can be applied following to genome mining for validation of data. Finally, we review on the literature describing all novel natural drugs isolated from bacteria, fungi, and other living organisms, not only from the marine environment, by a genome-mining approach, focusing on the literature available in the last ten years.

scholarly journals HEx: a heterologous expression platform for the discovery of fungal natural products

2018 ◽  
Author(s):  
Colin JB Harvey ◽  
Mancheng Tang ◽  
Ulrich Schlecht ◽  
Joe Horecka ◽  
Curt R Fischer ◽  
...  
Keyword(s):  
Natural Products ◽  
Synthetic Biology ◽  
Heterologous Expression ◽  
Gene Clusters ◽  
Fungal Species ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Expression Platform ◽  
The World ◽  
Fungal Natural Products

AbstractFor decades, fungi have been a source of FDA-approved natural products such as penicillin, cyclosporine, and the statins. Recent breakthroughs in DNA sequencing suggest that millions of fungal species exist on Earth with each genome encoding pathways capable of generating as many as dozens of natural products. However, the majority of encoded molecules are difficult or impossible to access because the organisms are uncultivable or the genes are transcriptionally silent. To overcome this bottleneck in natural product discovery, we developed the HEx (Heterologous EXpression) synthetic biology platform for rapid, scalable expression of fungal biosynthetic genes and their encoded metabolites in Saccharomyces cerevisiae. We applied this platform to 41 fungal biosynthetic gene clusters from diverse fungal species from around the world, 22 of which produced detectable compounds. These included novel compounds with unexpected biosynthetic origins, particularly from poorly studied species. This result establishes the HEx platform for rapid discovery of natural products from any fungal species, even those that are uncultivable, and opens the door to discovery of the next generation of natural products.SummaryHere we present the largest scale effort reported to date toward the complete refactoring and heterologous expression of fungal biosynthetic gene clusters utilizing HEx, a novel synthetic biology platform.

Recent Advance in Natural Products with Antiviral Activities

2021 ◽  
Vol 21 ◽  
Author(s):  
Zhi-Gang Sun ◽  
Zhi-Na Li ◽  
Xiang-Wan Miao ◽  
Shuang Li ◽  
Hai-Liang Zhu
Keyword(s):  
Natural Products ◽  
Nucleic Acid ◽  
Antiviral Activity ◽  
Infectious Diseases ◽  
Living Cells ◽  
Chemical Substances ◽  
The World ◽  
Antiviral Activities ◽  
Living Organisms ◽  
Epidemic Diseases

: Virus is a type of noncellular organism, which is simple in structure, small in size and contains only one kind of nucleic acid (RNA or DNA). It must be parasitized in living cells and proliferates by replication. Viruses can infect plants or animals, which leads to many epidemic diseases, such as the current pandemic COVID-19. Viral infectious diseases have brought serious threats to the health of people around the world. Natural products are chemical substances that are usually produced by living organisms and have biological or pharmacological activity. Many of these natural products show antiviral activity. Based on the increasing importance of antiviral research, this paper focuses on the discovery and development of antiviral natural products since 2010.

GENOTOXIC ACTIVITY OF THE PESTICIDE MIXTURES

2020 ◽  
pp. 9-13 ◽  
Author(s):  
N. A. Ilyushina ◽  
Yu. A. Revazova
Keyword(s):  
Public Health ◽  
Combined Effect ◽  
Literature Information ◽  
Genotoxic Effects ◽  
Antagonistic Effects ◽  
Pesticide Mixtures ◽  
The World ◽  
Living Organisms ◽  
Genetic Structures ◽  
Active Substances

In order to overcome resistance to individual pesticides and improve their effectiveness, formulations containing two or more active substances are constantly being developed and put on the market over recent years. Mixtures of residual amounts of pesticides can be present in water and food and enter the human and animal bodies. However, the combined effect of pesticides on living organisms, including genetic structures in cells, has not been studied enough and it is not yet possible to predict the genotoxic effects of their mixtures based on available data. The purpose of this review was to collect and summarize literature information on the genotoxicity of pesticide combinations obtained at different objects. The results of studies conducted in different countries of the world are discussed, examples of detected synergistic, additive and antagonistic effects are given, indicating the need for testing the genotoxicity of preparative forms of pesticides containing several active substances, as well as mixtures of jointly used pesticides in order to ensure the safe use of pesticides for public health.

scholarly journals The Emerging Global Tobacco Treatment Workforce: Characteristics of Tobacco Treatment Specialists Trained in Council-Accredited Training Programs from 2017 to 2019

2021 ◽  
Vol 18 (5) ◽  
pp. 2416
Author(s):  
Christine E. Sheffer ◽  
Abdulmohsen Al-Zalabani ◽  
Andrée Aubrey ◽  
Rasha Bader ◽  
Claribel Beltrez ◽  
...  
Keyword(s):  
North America ◽  
Tobacco Use ◽  
Training Programs ◽  
Systems Of Care ◽  
Eastern Mediterranean ◽  
Annual Number ◽  
Treatment Services ◽  
Tobacco Treatment ◽  
The World ◽  
Academic Settings

Tobacco use is projected to kill 1 billion people in the 21st century. Tobacco Use Disorder (TUD) is one of the most common substance use disorders in the world. Evidence-based treatment of TUD is effective, but treatment accessibility remains very low. A dearth of specially trained clinicians is a significant barrier to treatment accessibility, even within systems of care that implement brief intervention models. The treatment of TUD is becoming more complex and tailoring treatment to address new and traditional tobacco products is needed. The Council for Tobacco Treatment Training Programs (Council) is the accrediting body for Tobacco Treatment Specialist (TTS) training programs. Between 2016 and 2019, n = 7761 trainees completed Council-accredited TTS training programs. Trainees were primarily from North America (92.6%) and the Eastern Mediterranean (6.1%) and were trained via in-person group workshops in medical and academic settings. From 2016 to 2019, the number of Council-accredited training programs increased from 14 to 22 and annual number of trainees increased by 28.5%. Trainees have diverse professional backgrounds and work in diverse settings but were primarily White (69.1%) and female (78.7%) located in North America. Nearly two-thirds intended to implement tobacco treatment services in their setting; two-thirds had been providing tobacco treatment for 1 year or less; and 20% were sent to training by their employers. These findings suggest that the training programs are contributing to the development of a new workforce of TTSs as well as the development of new programmatic tobacco treatment services in diverse settings. Developing strategies to support attendance from demographically and geographically diverse professionals might increase the proportion of trainees from marginalized groups and regions of the world with significant tobacco-related inequities.

Biosynthesis and synthetic biology of psychoactive natural products

2021 ◽  
Author(s):  
Cooper S. Jamieson ◽  
Joshua Misa ◽  
Yi Tang ◽  
John M. Billingsley
Keyword(s):  
Natural Products ◽  
Synthetic Biology ◽  
Biological Activities ◽  
Engineering Applications ◽  
Pathway Discovery

The biosynthetic logic employed by Nature in the construction of psychoactive natural products is reviewed, in addition to biological activities, methodologies enabling pathway discovery, and engineering applications.

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