scholarly journals Genome-Based Studies of Marine Microorganisms to Maximize the Diversity of Natural Products Discovery for Medical Treatments

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Xin-Qing Zhao
Keyword(s):  
Natural Products ◽  
Genome Mining ◽  
Chemical Diversity ◽  
Genomic Research ◽  
Marine Microorganisms ◽  
Genomic Information ◽  
Medical Treatments ◽  
The Past ◽  
Drug Molecules ◽  
Natural Products Discovery

Marine microorganisms are rich source for natural products which play important roles in pharmaceutical industry. Over the past decade, genome-based studies of marine microorganisms have unveiled the tremendous diversity of the producers of natural products and also contributed to the efficiency of harness the strain diversity and chemical diversity, as well as the genetic diversity of marine microorganisms for the rapid discovery and generation of new natural products. In the meantime, genomic information retrieved from marine symbiotic microorganisms can also be employed for the discovery of new medical molecules from yet-unculturable microorganisms. In this paper, the recent progress in the genomic research of marine microorganisms is reviewed; new tools of genome mining as well as the advance in the activation of orphan pathways and metagenomic studies are summarized. Genome-based research of marine microorganisms will maximize the biodiscovery process and solve the problems of supply and sustainability of drug molecules for medical treatments.

scholarly journals Novel Alkaloids from Marine Actinobacteria: Discovery and Characterization

Marine Drugs ◽  
2021 ◽  
Vol 20 (1) ◽  
pp. 6
Author(s):  
Anne-Sofie De Rop ◽  
Jeltien Rombaut ◽  
Thomas Willems ◽  
Marilyn De Graeve ◽  
Lynn Vanhaecke ◽  
...  
Keyword(s):  
Natural Products ◽  
Therapeutic Potential ◽  
Genome Mining ◽  
Marine Actinobacteria ◽  
The Past ◽  
Microbial Extracts ◽  
Bioactive Secondary Metabolites ◽  
Experimental Approaches ◽  
Excellent Resource ◽  
Made In

The marine environment is an excellent resource for natural products with therapeutic potential. Its microbial inhabitants, often associated with other marine organisms, are specialized in the synthesis of bioactive secondary metabolites. Similar to their terrestrial counterparts, marine Actinobacteria are a prevalent source of these natural products. Here, we discuss 77 newly discovered alkaloids produced by such marine Actinobacteria between 2017 and mid-2021, as well as the strategies employed in their elucidation. While 12 different classes of alkaloids were unraveled, indoles, diketopiperazines, glutarimides, indolizidines, and pyrroles were most dominant. Discoveries were mainly based on experimental approaches where microbial extracts were analyzed in relation to novel compounds. Although such experimental procedures have proven useful in the past, the methodologies need adaptations to limit the chance of compound rediscovery. On the other hand, genome mining provides a different angle for natural product discovery. While the technology is still relatively young compared to experimental screening, significant improvement has been made in recent years. Together with synthetic biology tools, both genome mining and extract screening provide excellent opportunities for continued drug discovery from marine Actinobacteria.

Case studies on computer-based identification of natural products as lead molecules

2020 ◽  
Vol 5 (10) ◽  
Author(s):  
Conrad V. Simoben ◽  
Fidele Ntie-Kang ◽  
Dina Robaa ◽  
Wolfgang Sippl
Keyword(s):  
Natural Products ◽  
Virtual Screening ◽  
Experimental Validation ◽  
Chemical Space ◽  
Chemical Diversity ◽  
Computer Aided Drug Design ◽  
Drug Molecules ◽  
Success Stories ◽  
Computer Based ◽  
Experimental Approaches

AbstractThe development and application of computer-aided drug design/discovery (CADD) techniques (such as structured-base virtual screening, ligand-based virtual screening and neural networks approaches) are on the point of disintermediation in the pharmaceutical drug discovery processes. The application of these CADD methods are standing out positively as compared to other experimental approaches in the identification of hits. In order to venture into new chemical spaces, research groups are exploring natural products (NPs) for the search and identification of new hits and more efficient leads as well as the repurposing of approved NPs. The chemical space of NPs is continuously increasing as a result of millions of years of evolution of species and these data are mainly stored in the form of databases providing access to scientists around the world to conduct studies using them. Investigation of these NP databases with the help of CADD methodologies in combination with experimental validation techniques is essential to identify and propose new drug molecules. In this chapter, we highlight the importance of the chemical diversity of NPs as a source for potential drugs as well as some of the success stories of NP-derived candidates against important therapeutic targets. The focus is on studies that applied a healthy dose of the emerging CADD methodologies (structure-based, ligand-based and machine learning).

scholarly journals Recent Advances in Silent Gene Cluster Activation in Streptomyces

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhenyu Liu ◽  
Yatong Zhao ◽  
Chaoqun Huang ◽  
Yunzi Luo
Keyword(s):  
Natural Products ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Heterologous Host ◽  
Silent Gene ◽  
Drug Molecules ◽  
Discovery Research ◽  
Natural Products Discovery ◽  
Native Host

Natural products (NPs) are critical sources of drug molecules for decades. About two-thirds of natural antibiotics are produced by Streptomyces. Streptomyces have a large number of secondary metabolite biosynthetic gene clusters (SM-BGCs) that may encode NPs. However, most of these BGCs are silent under standard laboratory conditions. Hence, activation of these silent BGCs is essential to current natural products discovery research. In this review, we described the commonly used strategies for silent BGC activation in Streptomyces from two aspects. One focused on the strategies applied in heterologous host, including methods to clone and reconstruct BGCs along with advances in chassis engineering; the other focused on methods applied in native host which includes engineering of promoters, regulatory factors, and ribosomes. With the metabolic network being elucidated more comprehensively and methods optimized more high-thoroughly, the discovery of NPs will be greatly accelerated.

scholarly journals Recapitulation of the evolution of biosynthetic gene clusters reveals hidden chemical diversity on bacterial genomes

2015 ◽  
Author(s):  
Pablo Cruz-Morales ◽  
Christian E. Martínez-Guerrero ◽  
Marco A. Morales-Escalante ◽  
Luis Yáñez-Guerra ◽  
Johannes Florian Kopp ◽  
...  
Keyword(s):  
Natural Products ◽  
Chemical Space ◽  
Streptomyces Coelicolor ◽  
Genome Mining ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Chemical Diversity ◽  
Biosynthetic Gene ◽  
Bacterial Genomes ◽  
Biosynthetic Gene Clusters

AbstractNatural products have provided humans with antibiotics for millennia. However, a decline in the pace of chemical discovery exerts pressure on human health as antibiotic resistance spreads. The empirical nature of current genome mining approaches used for natural products research limits the chemical space that is explored. By integration of evolutionary concepts related to emergence of metabolism, we have gained fundamental insights that are translated into an alternative genome mining approach, termed EvoMining. As the founding assumption of EvoMining is the evolution of enzymes, we solved two milestone problems revealing unprecedented conversions. First, we report the biosynthetic gene cluster of the ‘orphan’ metabolite leupeptin in Streptomyces roseus. Second, we discover an enzyme involved in formation of an arsenic-carbon bond in Streptomyces coelicolor and Streptomyces lividans. This work provides evidence that bacterial chemical repertoire is underexploited, as well as an approach to accelerate the discovery of novel antibiotics from bacterial genomes.

scholarly journals Bioactive Secondary Metabolites from Octocoral-Associated Microbes—New Chances for Blue Growth

Marine Drugs ◽  
2018 ◽  
Vol 16 (12) ◽  
pp. 485 ◽  
Author(s):  
Inês Raimundo ◽  
Sandra Silva ◽  
Rodrigo Costa ◽  
Tina Keller-Costa
Keyword(s):  
Natural Products ◽  
Genome Mining ◽  
Gene Clusters ◽  
Chemical Diversity ◽  
Chemical Structures ◽  
Novel Drugs ◽  
Blue Growth ◽  
Microbial Symbionts ◽  
Bacteria And Fungi ◽  
Near Future

Octocorals (Cnidaria, Anthozoa Octocorallia) are magnificent repositories of natural products with fascinating and unusual chemical structures and bioactivities of interest to medicine and biotechnology. However, mechanistic understanding of the contribution of microbial symbionts to the chemical diversity of octocorals is yet to be achieved. This review inventories the natural products so-far described for octocoral-derived bacteria and fungi, uncovering a true chemical arsenal of terpenes, steroids, alkaloids, and polyketides with antibacterial, antifungal, antiviral, antifouling, anticancer, anti-inflammatory, and antimalarial activities of enormous potential for blue growth. Genome mining of 15 bacterial associates (spanning 12 genera) cultivated from Eunicella spp. resulted in the identification of 440 putative and classifiable secondary metabolite biosynthetic gene clusters (BGCs), encompassing varied terpene-, polyketide-, bacteriocin-, and nonribosomal peptide-synthase BGCs. This points towards a widespread yet uncharted capacity of octocoral-associated bacteria to synthetize a broad range of natural products. However, to extend our knowledge and foster the near-future laboratory production of bioactive compounds from (cultivatable and currently uncultivatable) octocoral symbionts, optimal blending between targeted metagenomics, DNA recombinant technologies, improved symbiont cultivation, functional genomics, and analytical chemistry are required. Such a multidisciplinary undertaking is key to achieving a sustainable response to the urgent industrial demand for novel drugs and enzyme varieties.

scholarly journals Coupling Mass Spectral and Genomic Information to Improve Bacterial Natural Product Discovery Workflows

Marine Drugs ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 142 ◽  
Author(s):  
Max Crüsemann
Keyword(s):  
Mass Spectrometry ◽  
Natural Products ◽  
Natural Product ◽  
Large Scale ◽  
Genome Mining ◽  
Structural Diversity ◽  
Gene Clusters ◽  
Genomic Information ◽  
Mass Spectral ◽  
Natural Product Discovery

Bacterial natural products possess potent bioactivities and high structural diversity and are typically encoded in biosynthetic gene clusters. Traditional natural product discovery approaches rely on UV- and bioassay-guided fractionation and are limited in terms of dereplication. Recent advances in mass spectrometry, sequencing and bioinformatics have led to large-scale accumulation of genomic and mass spectral data that is increasingly used for signature-based or correlation-based mass spectrometry genome mining approaches that enable rapid linking of metabolomic and genomic information to accelerate and rationalize natural product discovery. In this mini-review, these approaches are presented, and discovery examples provided. Finally, future opportunities and challenges for paired omics-based natural products discovery workflows are discussed.

scholarly journals Extending the “One Strain Many Compounds” (OSMAC) Principle to Marine Microorganisms

Marine Drugs ◽  
2018 ◽  
Vol 16 (7) ◽  
pp. 244 ◽  
Author(s):  
Stefano Romano ◽  
Stephen Jackson ◽  
Sloane Patry ◽  
Alan Dobson
Keyword(s):  
Secondary Metabolites ◽  
Nutrient Content ◽  
Gene Clusters ◽  
Chemical Diversity ◽  
Marine Microorganisms ◽  
Marine Microbes ◽  
Comprehensive Overview ◽  
Single Strain ◽  
The One ◽  
Natural Products Discovery

Genomic data often highlights an inconsistency between the number of gene clusters identified using bioinformatic approaches as potentially producing secondary metabolites and the actual number of chemically characterized secondary metabolites produced by any given microorganism. Such gene clusters are generally considered as “silent”, meaning that they are not expressed under laboratory conditions. Triggering expression of these “silent” clusters could result in unlocking the chemical diversity they control, allowing the discovery of novel molecules of both medical and biotechnological interest. Therefore, both genetic and cultivation-based techniques have been developed aimed at stimulating expression of these “silent” genes. The principles behind the cultivation based approaches have been conceptualized in the “one strain many compounds” (OSMAC) framework, which underlines how a single strain can produce different molecules when grown under different environmental conditions. Parameters such as, nutrient content, temperature, and rate of aeration can be easily changed, altering the global physiology of a microbial strain and in turn significantly affecting its secondary metabolism. As a direct extension of such approaches, co-cultivation strategies and the addition of chemical elicitors have also been used as cues to activate “silent” clusters. In this review, we aim to provide a focused and comprehensive overview of these strategies as they pertain to marine microbes. Moreover, we underline how changes in some parameters which have provided important results in terrestrial microbes, but which have rarely been considered in marine microorganisms, may represent additional strategies to awaken “silent” gene clusters in marine microbes. Unfortunately, the empirical nature of the OSMAC approach forces scientists to perform extensive laboratory experiments. Nevertheless, we believe that some computation and experimental based techniques which are used in other disciplines, and which we discuss; could be effectively employed to help streamline the OSMAC based approaches. We believe that natural products discovery in marine microorganisms would be greatly aided through the integration of basic microbiological approaches, computational methods, and technological innovations, thereby helping unearth much of the as yet untapped potential of these microorganisms.

scholarly journals Natural products discovery needs improved taxonomic and geographic information

2016 ◽  
Vol 33 (6) ◽  
pp. 747-750 ◽  
Author(s):  
Miguel C. Leal ◽  
Ana Hilário ◽  
Murray H. G. Munro ◽  
John W. Blunt ◽  
Ricardo Calado
Keyword(s):  
Natural Products ◽  
Geographic Information ◽  
Chemical Diversity ◽  
Chemical Products ◽  
Natural Products Discovery

Marine and terrestrial organisms yield a remarkable chemical diversity and are important sources for discovery of new chemical products.

8. Genome Guided Discovery of Chlorinated Natural Products in Streptomyces curacoi

2018 ◽  
Author(s):  
Stephanie Hrab
Keyword(s):  
Natural Products ◽  
Biological Activity ◽  
Staphylococcus Epidermidis ◽  
Genome Mining ◽  
Genomic Information ◽  
Guided Discovery ◽  
Genus Streptomyces ◽  
Bacterial Rna ◽  
Common Strategy ◽  
Halogenated Natural Products

Natural products derived from plants, animals, and microbes have long been a rich source of molecules that exhibit biological activity. Bacteria of the genus Streptomyces are one of the most important sources of natural products today, producing more than half of all known antibiotics. One class of natural products that have potent antibiotic activity are those that contain halogens. There are many examples of halogenated natural products such as the antibiotics vancomycin and chloramphenicol. Incorporation of halogen atoms into drugs is a common strategy to enhance their bioactivity and specificity. Rapid advances in DNA sequencing have led to genome mining approaches to discover new natural products. This technique can also be used to find bioactive halogenated products by analyzing the genomes for sequences encoding the ‘halogenases’ that are responsible for addition of the halogen. One class of compounds that have biological activity against Streptococcus pneumoniae, Staphylococcus aureus, and Staphylococcus epidermidis are the desotamides. These compounds inhibit bacterial RNA polymerases. A cluster of genes that is likely responsible for the production this compound has been discovered in the Streptomyces curacoi genome; however this cluster is unique in that it also contains a halogenase gene. This study aims to discover a halogenated desotamide derivative from Streptomyces curacoi based on the genomic information. It is hypothesized that this derivative will have enhanced or new biological activity.

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