Drug discovery from natural products (original) (raw)

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.

Bioactive Metabolites from Indigenous Actinomycetes Isolated from Marine Water

Journal of Pharmacy and Nutrition Sciences, 2015

Microbial natural products have continued to play an important role in the discovery of novel chemicals for the development of important therapeutic agents. Actinomycetes form a potent reservoir of biologically active secondary metabolites and enzymes. The need for finding novel bioactive compounds for the development of new therapeutic agents is required due to the emergence of antibiotic resistance among pathogenic bacteria. Actinomycetes are considered as one of the best producers of variety of antagonistic compounds that could serve as potential chemotherapeutic agents. The present study was undertaken to find new antagonistic compounds from actinomycetes. Actinomycetes were successfully isolated from marine water samples collected at various locations of Karachi. Initially 39 isolates were collected out of which 23 were found to produce active metabolites against one or more test bacterial cultures. Actinomycetes strains IS26, IS33, and IS39 showed significant potential of havi...

Bioactive compounds from marine actinomycetes

Indian Journal of Microbiology, 2008

Actinomycetes are one of the most effi cient groups of secondary metabolite producers and are very important from an industrial point of view. Among its various genera, Streptomyces, Saccharopolyspora, Amycolatopsis, Micromonospora and Actinoplanes are the major producers of commercially important biomolecules. Several species have been isolated and screened from the soil in the past decades. Consequently the chance of isolating a novel actinomycete strain from a terrestrial habitat, which would produce new biologically active metabolites, has reduced. The most relevant reason for discovering novel secondary metabolites is to circumvent the problem of resistant pathogens, which are no longer susceptible to the currently used drugs. Existence of actinomycetes has been reported in the hitherto untapped marine ecosystem. Marine actinomycetes are effi cient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, insecticidal and enzyme inhibition. Bioactive compounds from marine actinomycetes possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens.

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.

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.

Marine actinomycetes: An ongoing source of novel bioactive metabolites

Actinomycetes are virtually unlimited sources of novel compounds with many therapeutic applications and hold a prominent position due to their diversity and proven ability to produce novel bioactive compounds. There are more than 22,000 known microbial secondary metabolites, 70% of which are produced by actinomycetes, 20% from fungi, 7% from Bacillus spp. and 1-2% by other bacteria. Among the actinomycetes, streptomycetes group are considered economically important because out of the approximately more than 10,000 known antibiotics, 50-55% are produced by this genus. The ecological role of actinomycetes in the marine ecosystem is largely neglected and various assumptions meant there was little incentive to isolate marine strains for search and discovery of new drugs. The search for and discovery of rare and new actinomycetes is of significant interest to drug discovery due to a growing need for the development of new and potent therapeutic agents. Modern molecular technologies are adding strength to the target-directed search for detection and isolation of bioactive actinomycetes, and continued development of improved cultivation methods and molecular technologies for accessing the marine environment promises to provide access to this significant new source of chemical diversity with novel/rare actinomycetes including new species of previously reported actinomycetes.

Antitumor Compounds from Marine Actinomycetes

Marine Drugs, 2009

Chemotherapy is one of the main treatments used to combat cancer. A great number of antitumor compounds are natural products or their derivatives, mainly produced by microorganisms. In particular, actinomycetes are the producers of a large number of natural products with different biological activities, including antitumor properties. These antitumor compounds belong to several structural classes such as anthracyclines, enediynes, indolocarbazoles, isoprenoides, macrolides, non-ribosomal peptides and others, and they exert antitumor activity by inducing apoptosis through DNA cleavage mediated by topoisomerase I or II inhibition, mitochondria permeabilization, inhibition of key enzymes involved in signal transduction like proteases, or cellular metabolism and in some cases by inhibiting tumor-induced angiogenesis. Marine organisms have attracted special attention in the last years for their ability to produce interesting pharmacological lead compounds.

Update on Bioactive Molecules of Actinomycetes

Biosciences Biotechnology Research Asia, 2014

Marine and terrestrial regions are explored from many years and their bioactive compounds are being exploited. As the use of therapeutic novel compounds increases, researchers from all over the world started exploring oceans for bioactive compounds. Actinomycetes, filamentous bacteria have been extensively studied for their therapeutic compounds. They are found to occur in aquatic environments; freshwater and marine habitats. Mostly the marine actinomycetes have attracted a great attention as they have unique metabolic and physiological capabilities. Aquatic habitats enable them to survive in extremes of pressure, salinity and temperature, with the potential production of novel secondary metabolites not observed in actinomycetes, isolated from terrestrial habitats. Secondary metabolites produced from these actinomycetes viz. amino glycosides (streptomycin and kanamycin), ansamycins (rifampicin), anthracyclines (doxorubicin), blactam (cephalosporines), macrolides (erythromycin and tetracycline) and many others are considered to be bioactive. The biological diversity of actinomycetes is enormous in nature with diverse chemical compounds. These diverse chemical compounds have been responsible for great biological activities such as antimicrobial, antimalarial, antidiabetic, antitumor, antioxidant, insecticidal, antitubercular etc. Hence there is a scope of developing these bioactive metabolites as a potent therapeutic drug or lead compounds. However, the potential of actinomycetes is correctly studied though the exact wealth of these is unexplored.

Natural Products from Actinomycetes Associated with Marine Organisms

Marine Drugs, 2021

The actinomycetes have proven to be a rich source of bioactive secondary metabolites and play a critical role in the development of pharmaceutical researches. With interactions of host organisms and having special ecological status, the actinomycetes associated with marine animals, marine plants, macroalgae, cyanobacteria, and lichens have more potential to produce active metabolites acting as chemical defenses to protect the host from predators as well as microbial infection. This review focuses on 536 secondary metabolites (SMs) from actinomycetes associated with these marine organisms covering the literature to mid-2021, which will highlight the taxonomic diversity of actinomycetes and the structural classes, biological activities of SMs. Among all the actinomycetes listed, members of Streptomyces (68%), Micromonospora (6%), and Nocardiopsis (3%) are dominant producers of secondary metabolites. Additionally, alkaloids (37%), polyketides (33%), and peptides (15%) comprise the larg...

Molecular insights on the biosynthesis of antitumour compounds by actinomycetes

Microbial Biotechnology, 2011

Natural products are traditionally the main source of drug leads. In particular, many antitumour compounds are either natural products or derived from them. However, the search for novel antitumour drugs active against untreatable tumours, with fewer side-effects or with enhanced therapeutic efficiency, is a priority goal in cancer chemotherapy. Microorganisms, particularly actinomycetes, are prolific producers of bioactive compounds, including antitumour drugs, produced as secondary metabolites. Structural genes involved in the biosynthesis of such compounds are normally clustered together with resistance and regulatory genes, which facilitates the isolation of the gene cluster. The characterization of these clusters has represented, during the last 25 years, a great source of genes for the generation of novel derivatives by using combinatorial biosynthesis approaches: gene inactivation, gene expression, heterologous expression of the clusters or mutasynthesis. In addition, these techniques have been also applied to improve the production yields of natural and novel antitumour compounds. In this review we focus on some representative antitumour compounds produced by actinomycetes covering the genetic approaches used to isolate and validate their biosynthesis gene clusters, which finally led to generating novel derivatives and to improving the production yields.