Molecular insights on the biosynthesis of antitumour compounds by actinomycetes (original) (raw)
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Natural Product Reports, 2009
Antitumor compounds produced by actinomycetes and novel derivatives generated by combinatorial biosynthesis are reviewed (with 318 references cited). The different structural groups for which the relevant gene clusters have been isolated and characterized are reviewed, with a description of the strategies used for the generation of the novel derivatives and the activities of these compounds against tumor cell lines.
Reappraisal of actinomycetes for novel bioactive metabolites
Annals of Phytomedicine: An International Journal, 2017
The appearance of new deadly diseases like cancer and the burgeoning problem of drug resistance among common bacteria l pathogens are a serious threat to a vailable trea tments. Since the channels of compounds under development are limited, this necessitates the discovery of new drugs. It is where actinomycetes can complement in the accomplishment of development of thera peu tically new bioactive compounds, predomina ntly u sed in antibiotic production. Actinomycetes are diverse in their location and have proven ability to produce new bioactive compounds. By employing modern microbiological and molecular technologies, the target-directed search for detection and isolation of bioactive actinomycetes is gaining more strength. Therefore, the innova tive isolation of actinomycetes from extreme ecosystems, their identification and cultivation using novel techniques are imperative to pursue for drug discovery.
The rapid emergence of antioxidant among pathogens has led to a renewed interest to search for novel antioxidant potential of actinomycetes. Actinomycetes are enthralling resource due to their ability to produce novel bioactive secondary metabolites. They have proven to be an inexhaustive mine of Antioxidant, especially those potent against pathogenic organisms. Microbial secondary metabolites, especially those from actinomycetes have been a phenomenal success for the discovery of novel drugs. They produce a wide range of secondary metabolites and more than 70% of the naturally derived antibiotics are currently in clinical use. They remain a fundamental source of new chemical diversity and an important part of drug discovery. In the present study, actinomycetes were successfully isolated from soil sample using SCA medium. These organisms could be isolated with high frequency, without any contamination from the SCA. Pure culture was maintained in SCA. About eight strains of actinomycetes were isolated. Secondary metabolite extraction was performed by inoculating eight strains of actinomycetes in minimal media and incubating the flask for 10 days. The media was separated from the mycelia and extraction was done with ethyl acetate. The extract was collected and kept for air drying at room temperature for 2 days. The extract was screened for antioxidant and anticancer assay against MCF cancer lines. The extract showed high significant activity against the cancer cells.
FEBS Letters, 2012
Actinomycetes are a rich source for the synthesis of medically and technically useful natural products. The genes encoding the enzymes for their biosynthesis are normally organized in gene clusters, which include also the information for resistance (in the case of antibacterial compounds), regulation, and transport. This facilitates the manipulation of such pathways by molecular genetic techniques. Recent advances in DNA sequencing and analytical chemistry revealed that not only new strains isolated from yet unexplored habitats, but also already known strains possess a large potential for the synthesis of novel compounds. Synthetic Biology now offers a new perspective to exploit this potential further by generating novel pathways, and thereby novel products, by combining different biosynthetic steps originating from different bacteria. The supply of precursors, which are subsequently incorporated into the final product, is often already organized in a modular manner in nature and may directly be exploited for Synthetic Biology. Here we report examples for the synthesis of building blocks and possibilities to modify and optimize antibiotic biosynthesis, exemplary for the synthesis of the manipulation of the synthesis of the glycopeptide antibiotic balhimycin. (W. Wohlleben). FEBS Letters xxx (2012) xxx-xxx j o u r n a l h o m e p a g e : w w w . F E B S L e t t e r s . o r g Please cite this article in press as: Wohlleben, W., et al. Synthetic Biology of secondary metabolite biosynthesis in actinomycetes: Engineering precursor supply as a way to optimize antibiotic production. FEBS Lett. (2012), http://dx.
Current approaches to exploit actinomycetes as a source of novel natural products
Journal of Industrial Microbiology & Biotechnology, 2011
For decades, microbial natural products have been one of the major sources of novel drugs for pharmaceutical companies, and today all evidence suggests that novel molecules with potential therapeutic applications are still waiting to be discovered from these natural sources, especially from actinomycetes. Any appropriate exploitation of the chemical diversity of these microbial sources relies on proper understanding of their biological diversity and other related key factors that maximize the possibility of successful identification of novel molecules. Without doubt, the discovery of platensimycin has shown that microbial natural products can continue to deliver novel scaffolds if appropriate tools are put in place to reveal them in a cost-effective manner. Whereas today innovative technologies involving exploitation of uncultivated environmental diversity, together with chemical biology and in silico approaches, are seeing rapid development in natural products research, maximization of the chances of exploiting chemical diversity from microbial collections is still essential for novel drug discovery. This work provides an overview of the integrated approaches developed at the former Basic Research Center of Merck Sharp and Dohme in Spain to exploit the diversity and biosynthetic potential of actinomycetes, and includes some examples of those that were successfully applied to the discovery of novel antibiotics.
Actinomycetes: a yet inexhaustive source of bioactive secondary metabolites
2013
The rapid emergence of antimicrobial resistance among pathogens has led to a renewed interest to search for novel antimicrobial agents. The history of new drug discovery processes shows that novel skeletons have, in the majority of cases come from natural sources. This involves screening of microorganisms or plant extracts. They have been the source of, or inspiration for the development of chemical entities introduced as pharmaceutical. Among microorganisms, actinomycetes are enthralling resource due to their ability to produce novel bioactive secondary metabolites with antimicrobial activities. They have proven to be an inexhaustive mine of antimicrobial agents, especially those potent against pathogenic organisms. Microbial secondary metabolites, especially those from actinomycetes have been a phenomenal success for the discovery of novel drugs. They produce a wide range of secondary metabolites and more than 70% of the naturally derived antibiotics are currently in clinical use. They remain a fundamental source of new chemical diversity and an important part of drug discovery. Their ingenuity and immense industrial value is extremely noteworthy. The discovery of Streptomycin from actinomycetes has been imperative to the exploration of this group as a source of novel bioactive compounds. This group of organisms have produce antibiotics in different classes such as aminoglycosides, ansamycins, anthracyclines, glycopeptides, β-lactams, macrolides, nucleosides, peptides, polyenes, polyethers, and tetracyclines. Existence of actinomycetes has been reported in both terrestrial and marine habitats. This chapter highlight the bioactive metabolites produces by actinomycetes and their mode of action.
Bioprospecting of actinomycetes : Computational drug discovery approach
2017
There is an urgent need for new drugs with increasing threat posed by multidrug resistant bacteria. Among the various sources of natural products actinomycetes hold prominent position due to their diversity and proven ability to produce bioactive metabolites. Generally, analytical instrumentation and chemical methods are widely used to identify and characterize potent compounds, however, of late genomic based approach and metabolomics tools are used for metabolite screening. This article deals with computer aided databases, genome based analysis and metabolomics tools to identify, mine and characterize natural products. A systematic approach including construction of natural product libraries and their crude extracts, dereplication, genome mining, bioinformatics, activation of silent gene clusters and increasing the active compound by precision engineering can lead to novel and potent drugs.
Bioactive Metabolites from Terrestrial and Marine Actinomycetes
Molecules
Actinomycetes inhabit both terrestrial and marine ecosystems and are highly proficient in producing a wide range of natural products with diverse biological functions, including antitumor, immunosuppressive, antimicrobial, and antiviral activities. In this review, we delve into the life cycle, ecology, taxonomy, and classification of actinomycetes, as well as their varied bioactive metabolites recently discovered between 2015 and 2023. Additionally, we explore promising strategies to unveil and investigate new bioactive metabolites, encompassing genome mining, activation of silent genes through signal molecules, and co-cultivation approaches. By presenting this comprehensive and up-to-date review, we hope to offer a potential solution to uncover novel bioactive compounds with essential activities.