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 Natural product drug discovery in the artificial intelligence era

2022 ◽  
Author(s):  
Fernanda I Saldivar-Gonzalez ◽  
Victor Daniel Aldas-Bulos ◽  
José Luis Medina-Franco ◽  
Fabien Plisson
Keyword(s):  
Artificial Intelligence ◽  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
Drug Targets ◽  
Structural Diversity ◽  
Protein Drug ◽  
Privileged Structures

Natural products (NPs) are primarily recognized as privileged structures to interact with protein drug targets. Their unique characteristics and structural diversity continue to marvel scientists for developing NP-inspired medicines, even...

scholarly journals Modern Approaches in the Discovery and Development of Plant-Based Natural Products and Their Analogues as Potential Therapeutic Agents

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 349
Author(s):  
Asim Najmi ◽  
Sadique A. Javed ◽  
Mohammed Al Bratty ◽  
Hassan A. Alhazmi
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
Therapeutic Agents ◽  
Throughput Capacity ◽  
Scientific Interest ◽  
Comprehensive Overview ◽  
Natural Sources ◽  
Discovery Research ◽  
Drug Discovery Research

Natural products represents an important source of new lead compounds in drug discovery research. Several drugs currently used as therapeutic agents have been developed from natural sources; plant sources are specifically important. In the past few decades, pharmaceutical companies demonstrated insignificant attention towards natural product drug discovery, mainly due to its intrinsic complexity. Recently, technological advancements greatly helped to address the challenges and resulted in the revived scientific interest in drug discovery from natural sources. This review provides a comprehensive overview of various approaches used in the selection, authentication, extraction/isolation, biological screening, and analogue development through the application of modern drug-development principles of plant-based natural products. Main focus is given to the bioactivity-guided fractionation approach along with associated challenges and major advancements. A brief outline of historical development in natural product drug discovery and a snapshot of the prominent natural drugs developed in the last few decades are also presented. The researcher’s opinions indicated that an integrated interdisciplinary approach utilizing technological advances is necessary for the successful development of natural products. These involve the application of efficient selection method, well-designed extraction/isolation procedure, advanced structure elucidation techniques, and bioassays with a high-throughput capacity to establish druggability and patentability of phyto-compounds. A number of modern approaches including molecular modeling, virtual screening, natural product library, and database mining are being used for improving natural product drug discovery research. Renewed scientific interest and recent research trends in natural product drug discovery clearly indicated that natural products will play important role in the future development of new therapeutic drugs and it is also anticipated that efficient application of new approaches will further improve the drug discovery campaign.

scholarly journals Natural Products as Modulators of Sirtuins

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3287 ◽  
Author(s):  
Berin Karaman Mayack ◽  
Wolfgang Sippl ◽  
Fidele Ntie-Kang
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Histone Deacetylases ◽  
High Throughput Screening ◽  
Chemical Space ◽  
Class Iii ◽  
Drug Candidates ◽  
Starting Point ◽  
Recent Developments ◽  
Potent Drug

Natural products have been used for the treatment of human diseases since ancient history. Over time, due to the lack of precise tools and techniques for the separation, purification, and structural elucidation of active constituents in natural resources there has been a decline in financial support and efforts in characterization of natural products. Advances in the design of chemical compounds and the understanding of their functions is of pharmacological importance for the biomedical field. However, natural products regained attention as sources of novel drug candidates upon recent developments and progress in technology. Natural compounds were shown to bear an inherent ability to bind to biomacromolecules and cover an unparalleled chemical space in comparison to most libraries used for high-throughput screening. Thus, natural products hold a great potential for the drug discovery of new scaffolds for therapeutic targets such as sirtuins. Sirtuins are Class III histone deacetylases that have been linked to many diseases such as Parkinson`s disease, Alzheimer’s disease, type II diabetes, and cancer linked to aging. In this review, we examine the revitalization of interest in natural products for drug discovery and discuss natural product modulators of sirtuins that could serve as a starting point for the development of isoform selective and highly potent drug-like compounds, as well as the potential application of naturally occurring sirtuin inhibitors in human health and those in clinical trials.

A primer on natural product-based virtual screening

2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Eleni Koulouridi ◽  
Marilia Valli ◽  
Fidele Ntie-Kang ◽  
Vanderlan da Silva Bolzani
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Molecular Modeling ◽  
Virtual Screening ◽  
Natural Product ◽  
General Purpose ◽  
Target Type ◽  
Computational Techniques ◽  
Specific Subset ◽  
Virtual Libraries

Abstract Databases play an important role in various computational techniques, including virtual screening (VS) and molecular modeling in general. These collections of molecules can contain a large amount of information, making them suitable for several drug discovery applications. For example, vendor, bioactivity data or target type can be found when searching a database. The introduction of these data resources and their characteristics is used for the design of an experiment. The description of the construction of a database can also be a good advisor for the creation of a new one. There are free available databases and commercial virtual libraries of molecules. Furthermore, a computational chemist can find databases for a general purpose or a specific subset such as natural products (NPs). In this chapter, NP database resources are presented, along with some guidelines when preparing an NP database for drug discovery purposes.

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 UsingDrosophilaas a platform for drug discovery from natural products in Parkinson's disease

MedChemComm ◽  
2019 ◽  
Vol 10 (6) ◽  
pp. 867-879 ◽  
Author(s):  
Urmila Maitra ◽  
Lukasz Ciesla
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Natural Products ◽  
Drug Discovery ◽  
Therapeutic Potential ◽  
Natural Extracts ◽  
New Drug ◽  
Screening Platform ◽  
Drug Leads

The review provides an overview of discovery of new drug leads from natural extracts usingDrosophilaas a screening platform to evaluate the therapeutic potential of phytochemicals against Parkinson's disease.

scholarly journals Microbial Natural Products in Drug Discovery

Processes ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 470
Author(s):  
Ahmed S. Abdel-Razek ◽  
Mehrez E. El-Naggar ◽  
Ahmed Allam ◽  
Osama M. Morsy ◽  
Sarah I. Othman
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Human Life ◽  
Emerging Diseases ◽  
Plant Resources ◽  
Political Factors ◽  
Traditional Medicines ◽  
History Of ◽  
Cardiac Disorders ◽  
Microbial Natural Products

Over a long period of time, humans have explored many natural resources looking for remedies of various ailments. Traditional medicines have played an intrinsic role in human life for thousands of years, with people depending on medicinal plants and their products as dietary supplements as well as using them therapeutically for treatment of chronic disorders, such as cancer, malaria, diabetes, arthritis, inflammation, and liver and cardiac disorders. However, plant resources are not sufficient for treatment of recently emerging diseases. In addition, the seasonal availability and other political factors put constrains on some rare plant species. The actual breakthrough in drug discovery came concurrently with the discovery of penicillin from Penicillium notatum in 1929. This discovery dramatically changed the research of natural products and positioned microbial natural products as one of the most important clues in drug discovery due to availability, variability, great biodiversity, unique structures, and the bioactivities produced. The number of commercially available therapeutically active compounds from microbial sources to date exceeds those discovered from other sources. In this review, we introduce a short history of microbial drug discovery as well as certain features and recent research approaches, specifying the microbial origin, their featured molecules, and the diversity of the producing species. Moreover, we discuss some bioactivities as well as new approaches and trends in research in this field.

scholarly journals Bridging the gap between natural product synthesis and drug discovery

2020 ◽  
Vol 37 (11) ◽  
pp. 1436-1453 ◽  
Author(s):  
Nathanyal J. Truax ◽  
Daniel Romo
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
Chemical Space ◽  
Natural Product Synthesis ◽  
Chemical Information

Various synthetic strategies have been developed to explore natural products as an enduring source of chemical information useful for probing biological relevant chemical space and impacting drug discovery.

Harnessing the potential of natural products in drug discovery from a cheminformatics vantage point

2017 ◽  
Vol 15 (44) ◽  
pp. 9275-9282 ◽  
Author(s):  
Tiago Rodrigues
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
Product Space ◽  
Vantage Point

Cheminformatics tools provide a viable means to unravel chemistry and biology in natural product space.

Genome-Guided Discovery of Natural Products and Biosynthetic Pathways from Australia’s Untapped Microbial Megadiversity

2016 ◽  
Vol 69 (2) ◽  
pp. 129 ◽  
Author(s):  
John A. Kalaitzis ◽  
Shane D. Ingrey ◽  
Rocky Chau ◽  
Yvette Simon ◽  
Brett A. Neilan
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Genome Sequencing ◽  
Dna Sequences ◽  
Gene Clusters ◽  
Biosynthetic Pathways ◽  
Natural Product Biosynthesis ◽  
Guided Discovery ◽  
Biosynthesis Gene ◽  
Microbial Natural Products

Historically microbial natural product biosynthesis pathways were elucidated mainly by isotope labelled precursor directed feeding studies. Now the genetics underpinning the assembly of microbial natural products biosynthesis is so well understood that some pathways and their products can be predicted from DNA sequences alone. The association between microbial natural products and their biosynthesis gene clusters is now driving the field of ‘genetics guided natural product discovery’. This account overviews our research into cyanotoxin biosynthesis before the genome sequencing era through to some recent discoveries resulting from the mining of Australian biota for natural product biosynthesis pathways.

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