scholarly journals Exploring the Exceptional Properties of Streptomyces: A Hands-On Discovery of Natural Products

2019 ◽  
Vol 81 (9) ◽  
pp. 658-664
Author(s):  
María Inés Lapaz ◽  
Estefania Juarez Cisneros ◽  
María Julia Pianzzola ◽  
Isolde M. Francis
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Real Life ◽  
Bacterial Challenge ◽  
Microbial Biodiversity ◽  
Streptomyces Species ◽  
Hands On ◽  
Experimental Process ◽  
Metabolic Properties ◽  
Selection Of

Microbial biodiversity and its rich arsenal of natural products is an important and complex biological concept. We propose the use of Streptomyces, one of the most diverse bacterial genera and a major inhabitant of soil, as a model to explain the relevance and importance of this concept. Students will perform experiments ranging from isolation and selection of Streptomyces species, to performing fungal and bacterial challenge assays to evaluate their biocontrol capacity, to screening for specialized metabolic properties such as the production of lipases, amylases, and cellulases. Accompanied by active discussions on the experimental process and results, and integrated into the general microbiology curriculum, this real-life discovery-based lab exercise engages students in current topics concerning natural product discovery and reinforces their understanding of several important concepts in microbiology and biotechnology.

scholarly journals Cheminformatics Analysis of Natural Product Scaffolds: Comparison of Scaffolds Produced by Animals, Plants, Fungi and Bacteria

2020 ◽  
Author(s):  
Peter Ertl ◽  
Tim Schuhmann
Keyword(s):  
Natural Products ◽  
Natural Selection ◽  
Natural Product ◽  
Selection Process ◽  
Structural Features ◽  
New Drugs ◽  
Large Database ◽  
Biologically Relevant ◽  
Different Types ◽  
Selection Of

AbstractNatural products (NPs) have evolved over a very long natural selection process to form optimal interactions with biologically relevant macromolecules. NPs are therefore an extremely useful source of inspiration for the design of new drugs. In the present study we report the results of a cheminformatics analysis of a large database of NP structures focusing on their scaffolds. First, general differences between NP scaffolds and scaffolds from synthetic molecules are discussed, followed by a comparison of the properties of scaffolds produced by different types of organisms. Scaffolds produced by plants are the most complex and those produced by bacteria differ in many structural features from scaffolds produced by other organisms. The results presented here may be used as a guidance in selection of scaffolds for the design of novel NP-like bioactive structures or NP-inspired libraries.

scholarly journals Selection of Priority Natural Products for Evaluation as Potential Precipitants of Natural Product–Drug Interactions: A NaPDI Center Recommended Approach

2018 ◽  
Vol 46 (7) ◽  
pp. 1046-1052 ◽  
Author(s):  
Emily J. Johnson ◽  
Vanessa González-Peréz ◽  
Dan-Dan Tian ◽  
Yvonne S. Lin ◽  
Jashvant D. Unadkat ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Interactions ◽  
Natural Product ◽  
Selection Of

Unleashing the Potential of Microbial Natural Products in Drug Discovery: Focusing on Streptomyces as Antimicrobials Goldmine

2021 ◽  
Vol 21 ◽  
Author(s):  
Himangini Bansal ◽  
Rajeev K. Singla ◽  
Sahar Behzad ◽  
Hitesh Chopra ◽  
Ajmer S. Grewal ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
Therapeutic Potential ◽  
Streptomyces Species ◽  
New Era ◽  
Screening Programs ◽  
Starting Point ◽  
Privileged Structures ◽  
Microbial Natural Products

: The natural product specialized metabolites produced by microbes and plants are the backbone of our current drugs. Ironically, we are in a golden age of understanding natural product biosynthesis, biochemistry, and engineering. These advances have the potential to usher in a new era of natural product exploration and development, taking full advantage of the unique and favorable properties of natural product compounds in drug discovery. There is now an increasing realization that these privileged structures represent the optimal starting point for the development of clinically viable assets. Here, we outline the current state-of-the-art in antimicrobial natural product drug discovery, specifically Streptomyces species, with a specific focus on how the emerging field of synthetic biology is delivering the tools and technologies required to unlock the therapeutic potential of natural products. We illustrate how these approaches are circumventing many of the problems that have historically plagued conventional screening programs, enabling the expedient discovery of new molecules with novel functions.

scholarly journals Dissolution of the Disparate: Co-ordinate Regulation in Antibiotic Biosynthesis

Antibiotics ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 83 ◽  
Author(s):  
Thomas C. McLean ◽  
Barrie Wilkinson ◽  
Matthew I. Hutchings ◽  
Rebecca Devine
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Gene Clusters ◽  
Regulatory Control ◽  
Antibiotic Biosynthesis ◽  
Streptomyces Species ◽  
Natural Product Discovery ◽  
Intergenic Regions ◽  
Control Compound ◽  
The Impact

Discovering new antibiotics is vital to combat the growing threat of antimicrobial resistance. Most currently used antibiotics originate from the natural products of actinomycete bacteria, particularly Streptomyces species, that were discovered over 60 years ago. However, genome sequencing has revealed that most antibiotic-producing microorganisms encode many more natural products than previously thought. Biosynthesis of these natural products is tightly regulated by global and cluster situated regulators (CSRs), most of which respond to unknown environmental stimuli, and this likely explains why many biosynthetic gene clusters (BGCs) are not expressed under laboratory conditions. One approach towards novel natural product discovery is to awaken these cryptic BGCs by re-wiring the regulatory control mechanism(s). Most CSRs bind intergenic regions of DNA in their own BGC to control compound biosynthesis, but some CSRs can control the biosynthesis of multiple natural products by binding to several different BGCs. These cross-cluster regulators present an opportunity for natural product discovery, as the expression of multiple BGCs can be affected through the manipulation of a single regulator. This review describes examples of these different mechanisms, including specific examples of cross-cluster regulation, and assesses the impact that this knowledge may have on the discovery of novel natural products.

Synthesis and Biological Evaluation of the Antimicrobial Natural Product Lipoxazolidinone A

2018 ◽  
Author(s):  
Jonathan J. Mills ◽  
Kaylib R. Robinson ◽  
Troy E. Zehnder ◽  
Joshua G. Pierce
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Mechanism Of Action ◽  
Marine Natural Products ◽  
Biological Evaluation ◽  
Lead Compounds ◽  
Follow Up Studies ◽  
Initial Resistance ◽  
Synthesis And Biological Evaluation

The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogs to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.

Unzipping Natural Products: Improved Natural Product Structure Predictions by Ensemble Modeling and Fingerprint Matching

2018 ◽  
Author(s):  
William A. Shirley ◽  
Brian P. Kelley ◽  
Yohann Potier ◽  
John H. Koschwanez ◽  
Robert Bruccoleri ◽  
...  
Keyword(s):  
Natural Products ◽  
Open Source ◽  
Natural Product ◽  
Gene Cluster ◽  
Public Domain ◽  
Product Structure ◽  
Fingerprint Matching ◽  
Ensemble Modeling ◽  
Chemical Structures ◽  
Source Gene

This pre-print explores ensemble modeling of natural product targets to match chemical structures to precursors found in large open-source gene cluster repository antiSMASH. Commentary on method, effectiveness, and limitations are enclosed. All structures are public domain molecules and have been reviewed for release.

Recent Progress Towards Synthesis of the Indolizidine Alkaloid 195B

2020 ◽  
Vol 17 (2) ◽  
pp. 82-90 ◽  
Author(s):  
Ghodsi Mohammadi Ziarani ◽  
Fatemeh Mohajer ◽  
Zohreh kheilkordi
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Recent Progress ◽  
Human Life ◽  
Natural Compounds ◽  
Biologically Active ◽  
Pharmaceutical Chemistry ◽  
Biological Perspective ◽  
Highly Active

Background: Natural products have been received attention due to their importance in human life as those are biologically active. In this review, there are some reports through different methods related to the synthesis of the indolizidine 195B which was extracted from poisonous frog; however, due to respect nature, the synthesis of natural compounds such as indolizidine has been attracted much attention among scientists and researchers. Objective: This review discloses the procedures and methods to provide indolizidine 195B from 1989 to 2018 due to their importance as a natural product. Conclusion: There are several methods to give rise to the indolizidine 195B as a natural product that is highly active from the biological perspective in pharmaceutical chemistry. In summary, many protocols for the preparations of indolizidine 195B from various substrates, several reagents, and conditions have been reported from different aromatic and aliphatic.

Recent applications of asymmetric organocatalytic annulation reactions in natural product synthesis

2021 ◽  
Author(s):  
Nengzhong Wang ◽  
Zugen Wu ◽  
Junjie Wang ◽  
Nisar Ullah ◽  
Yixin Lu
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Natural Product Synthesis ◽  
Natural Products Synthesis

A comprehensive and updated summary of asymmetric organocatalytic annulation reactions is presented; in particular, the applications of these annulation strategies to natural products synthesis are highlighted.

scholarly journals Chemical Elicitors Induce Rare Bioactive Secondary Metabolites in Deep-Sea Bacteria under Laboratory Conditions

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 107
Author(s):  
Rafael de Felício ◽  
Patricia Ballone ◽  
Cristina Freitas Bazzano ◽  
Luiz F. G. Alves ◽  
Renata Sigrist ◽  
...  
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Natural Product ◽  
Deep Sea ◽  
Chemical Space ◽  
Bacterial Genome ◽  
Vast Number ◽  
Bacterial Metabolites ◽  
Laboratory Conditions ◽  
Deep Sea Bacteria

Bacterial genome sequencing has revealed a vast number of novel biosynthetic gene clusters (BGC) with potential to produce bioactive natural products. However, the biosynthesis of secondary metabolites by bacteria is often silenced under laboratory conditions, limiting the controlled expression of natural products. Here we describe an integrated methodology for the construction and screening of an elicited and pre-fractionated library of marine bacteria. In this pilot study, chemical elicitors were evaluated to mimic the natural environment and to induce the expression of cryptic BGCs in deep-sea bacteria. By integrating high-resolution untargeted metabolomics with cheminformatics analyses, it was possible to visualize, mine, identify and map the chemical and biological space of the elicited bacterial metabolites. The results show that elicited bacterial metabolites correspond to ~45% of the compounds produced under laboratory conditions. In addition, the elicited chemical space is novel (~70% of the elicited compounds) or concentrated in the chemical space of drugs. Fractionation of the crude extracts further evidenced minor compounds (~90% of the collection) and the detection of biological activity. This pilot work pinpoints strategies for constructing and evaluating chemically diverse bacterial natural product libraries towards the identification of novel bacterial metabolites in natural product-based drug discovery pipelines.

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