StreptomeDB 3.0: an updated compendium of streptomycetes natural products (original) (raw)
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StreptomeDB 2.0—an extended resource of natural products produced by streptomycetes
Over the last decades, the genus Streptomyces has stirred huge interest in the scientific community as a source of bioactive compounds. The majority of all known antibiotics is isolated from these bacterial strains, as well as a variety of other drugs such as antitumor agents, immunosuppressants and antifungals. To the best of our knowledge, StreptomeDB was the first database focusing on compounds produced by streptomycetes. The new version presented herein represents a major step forward: its content has been increased to over 4000 compounds and more than 2500 host organisms. In addition, we have extended the background information and included hundreds of new manually curated references to literature. The latest update features a unique scaffold-based navigation system, which enables the exploration of the chemical diversity of StreptomeDB on a structural basis. We have included a phylogenetic tree, based on 16S rRNA sequences, which comprises more than two-thirds of the included host organisms. It enables visualizing the frequency, appearance, and persistence of compounds and scaffolds in an evolutionary context. Additionally, we have included predicted MS- and NMR-spectra of thousands of compounds for assignment of experimental data. The database is freely accessible via http://www.pharmaceutical-bioinformatics.org/streptomedb.
StreptomeDB: a resource for natural compounds isolated from Streptomyces species
Nucleic acids research, 2013
Bacteria from the genus Streptomyces are very important for the production of natural bioactive compounds such as antibiotic, antitumor or immunosuppressant drugs. Around two thirds of all known natural antibiotics are produced by these bacteria. An enormous quantity of crucial data related to this genus has been generated and published, but so far no freely-available and comprehensive database exists. Here, we present StreptomeDB (http://www.pharmaceutical-bioinformatics.de/streptomedb/). To the best of our knowledge this is the largest database of natural products isolated from Streptomyces. It contains more than 2,400 unique and diverse compounds from more than 1,900 different Streptomyces strains and substrains. In addition to names and molecular structures of the compounds, information about source organisms, references, biological role, activities, and synthesis-routes (e.g. polyketide synthase (PKS)-derived, non-ribosomal peptides (NRPs)-derived) is included. Data can be accessed via queries on compound names, chemical structures, or organisms. Extraction from literature was performed through automatic text mining of thousands of articles from PubMed, followed by manual curation. All annotated compound structures can be downloaded from the website and applied for in silico screenings for identifying new active molecules with undiscovered properties.
Streptomyces from traditional medicine: sources of new innovations in antibiotic discovery
Journal of Medical Microbiology, 2020
Given the increased reporting of multi-resistant bacteria and the shortage of newly approved medicines, researchers have been looking towards extreme and unusual environments as a new source of antibiotics. Streptomyces currently provides many of the world’s clinical antibiotics, so it comes as no surprise that these bacteria have recently been isolated from traditional medicine. Given the wide array of traditional medicines, it is hoped that these discoveries can provide the much sought after core structure diversity that will be required of a new generation of antibiotics. This review discusses the contribution of Streptomyces to antibiotics and the potential of newly discovered species in traditional medicine. We also explore how knowledge of traditional medicines can aid current initiatives in sourcing new and chemically diverse antibiotics.
Journal of Pharmaceutical Research International
The ever-increasing fatality due to the surge of drug resistance has demanded the development of therapeutic metabolites with novel modes of mechanism. Despite the discovery of new antimicrobials, antibiotic resistance is increasing at an alarming rate. The emergence of novel molecules is necessary for targeting the Multidrug (MDR) and Pan-Drug resistant (PDR) pathogens which are the principal cause of life-threatening infections. Streptomyces strains commonly found in the soil produce secondary metabolites which have outstanding potential for being an antifungal and antibacterial agent. This study aims to isolate, identify, and characterize Streptomyces strains isolated from soil and extract their crude metabolites to determine their hidden therapeutic property. Out of four isolates identified, Streptomyces peucetius and Streptomyces lavendulae have shown significant antimicrobial activity against test organisms. To further determine the activity of their extracts GC-MS analysis, a...
Antibiotics
The overuse of antibiotics has resulted in the emergence of antibiotic resistance, not only in bacteria but also in fungi. Streptomyces are known to produce numerous secondary metabolites including clinically useful antibiotics. In this study, we screened for antibiotic-producing actinobacteria from soils in Taipei and discovered a Streptomyces strain SC26 that displayed antimicrobial activities against Gram-positive bacteria and fungi, but the compounds are heat-labile. Upon UV mutagenesis, a late-sporulation mutant SC263 was isolated with the same antibiotic spectrum but increased in thermostability. The nature of the antibiotic is not clear, but its activity was resistant to proteolytic, nucleolytic and pancreatic digestions, and was retained by the 100 kDa membrane during filtration. To gather more information on SC263, the genome was sequenced, which produced three contigs with a total of 8.2 Mb and was assigned to the species of Streptomyces spororaveus based on the average nu...
Streptomyces: Still the Biggest Producer of New Natural Secondary Metabolites, A Current Perspective
Microbiology Research
There is a real consensus that new antibiotics are urgently needed and are the best chance for combating antibiotic resistance. The phylum Actinobacteria is one of the main producers of new antibiotics, with a recent paradigm shift whereby rare actinomycetes have been increasingly targeted as a source of new secondary metabolites for the discovery of new antibiotics. However, this review shows that the genus Streptomyces is still the largest current producer of new and innovative secondary metabolites. Between January 2015 and December 2020, a significantly high number of novel Streptomyces spp. have been isolated from different environments, including extreme environments, symbionts, terrestrial soils, sediments and also from marine environments, mainly from marine invertebrates and marine sediments. This review highlights 135 new species of Streptomyces during this 6-year period with 108 new species of Streptomyces from the terrestrial environment and 27 new species from marine so...
Toward a new focus in antibiotic and drug discovery from the Streptomyces arsenal
Frontiers in Microbiology, 2015
Emergence of antibiotic resistant pathogens is changing the way scientists look for new antibiotic compounds. This race against the increased prevalence of multi-resistant strains makes it necessary to expedite the search for new compounds with antibiotic activity and to increase the production of the known. Here, we review a variety of new scientific approaches aiming to enhance antibiotic production in Streptomyces. These include: (i) elucidation of the signals that trigger the antibiotic biosynthetic pathways to improve culture media, (ii) bacterial hormone studies aiming to reproduce intra and interspecific communications resulting in antibiotic burst, (iii) co-cultures to mimic competition-collaboration scenarios in nature, and (iv) the very recent in situ search for antibiotics that might be applied in Streptomyces natural habitats. These new research strategies combined with new analytical and molecular techniques should accelerate the discovery process when the urgency for new compounds is higher than ever.
Genome Mining of Streptomyces sp. YIM 130001 Isolated From Lichen Affords New Thiopeptide Antibiotic
Frontiers in Microbiology, 2018
Streptomyces bacteria are recognized as an important source for antibiotics with broad applications in human medicine and animal health. Here, we report the isolation of a new lichen-associating Streptomyces sp. YIM 130001 from the tropical rainforest in Xishuangbanna (Yunnan, China), which displayed antibacterial activity against Bacillus subtilis. The draft genome sequence of this isolate strain revealed 18 putative biosynthetic gene clusters (BGCs) for secondary metabolites, which is an unusually low number compared to a typical streptomycete. Inactivation of a lantibiotic dehydrogenase-encoding gene from the BGC presumed to govern biosynthesis of a thiopeptide resulted in the loss of bioactivity. Using comparative HPLC analysis, two peaks in the chromatogram were identified in the extract from the wild-type strain, which were missing in the extract from the mutant. The compounds corresponding to the identified peaks were purified, and structure of one compound was elucidated using NMR. The compound, designated geninthiocin B, showed high similarity to several 35membered macrocyclic thiopeptides geninthiocin, Val-geninthiocin and berninamycin A. Bioinformatics analysis of the geninthiocin B BGC revealed its close homology to that of berninamycins.
Processes
Finding new antibacterial agents from natural products is urgently necessary to address the growing cases of antibiotic-resistant pathogens. Actinomycetes are regarded as an excellent source of therapeutically important secondary metabolites including antibiotics. However, they have not yet been characterized and explored in great detail for their utility in developing countries such as Nepal. In silico molecular docking in addition to antimicrobial assays have been used to examine the efficacy of chemical scaffolds biosynthesized by actinomycetes. This paper depicts the characterization of actinomycetes based on their morphology, biochemical tests, and partial molecular sequencing. Furthermore, antimicrobial assays and mass spectrometry-based metabolic profiling of isolates were studied. Seventeen actinomycete-like colonies were isolated from ten soil samples, of which three isolates showed significant antimicrobial activities. Those isolates were subsequently identified to be Stre...