scholarly journals Genome Mining Reveals Secondary Metabolites of Antarctic Bacterium Streptomyces Albidoflavus ANT_B131 Related to Antimicrobial and Antiproliferative Activities

Author(s):  
Paula de França ◽  
Jonas Costa ◽  
Taícia Fill ◽  
Marcelo Lancelotti ◽  
Ana Ruiz ◽  
...  

Abstract The antimicrobial resistance requires the urgent mining of new antimicrobials. Actinobacteria, specially Streptomyces genus, are responsible for production of numerous clinical antibiotics and anticancer agents. The use of genome mining can reveal the genetic potential of a strain to produce natural products, however the potential may not be express under laboratory conditions. In the present study, the Antarctic bacterium was taxonomically affiliated as Streptomyces albidoflavus, ANT_B131. The crude extracts showed antimicrobial activity against fungi, Gram-positive and Gram-negative bacteria and antiproliferative activity against five human tumor cell lines. Whole genome sequencing reveals a 6.96 Mb genome size and the genome mining showed 24 BGCs, representing 13.3% of the genome. The use of three culture media and extraction methods reveal the expression and recovery of 20% of the BGCs. The natural products identified were surugamide A, surugamide D, desferrioxamine B + Al, desferrioxamine E, and ectoine. This study reveals the potential of S. albidoflavus ANT_B131 as a natural product producer. Yet, the diversity of culture media and extraction methods could enhance the BGCs expression and recovery of natural products, and could be a new strategy to intensify the BGC expression of natural products.

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 199 ◽  
Author(s):  
Luisa Albarano ◽  
Roberta Esposito ◽  
Nadia Ruocco ◽  
Maria Costantini

Drug discovery is based on bioactivity screening of natural sources, traditionally represented by bacteria fungi and plants. Bioactive natural products and their secondary metabolites have represented the main source for new therapeutic agents, used as drug leads for new antibiotics and anticancer agents. After the discovery of the first biosynthetic genes in the last decades, the researchers had in their hands the tool to understand the biosynthetic logic and genetic basis leading to the production of these compounds. Furthermore, in the genomic era, in which the number of available genomes is increasing, genome mining joined to synthetic biology are offering a significant help in drug discovery. In the present review we discuss the importance of genome mining and synthetic biology approaches to identify new natural products, also underlining considering the possible advantages and disadvantages of this technique. Moreover, we debate the associated techniques that can be applied following to genome mining for validation of data. Finally, we review on the literature describing all novel natural drugs isolated from bacteria, fungi, and other living organisms, not only from the marine environment, by a genome-mining approach, focusing on the literature available in the last ten years.


Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5319
Author(s):  
Wamidh H. Talib ◽  
Izzeddin Alsalahat ◽  
Safa Daoud ◽  
Reem Fawaz Abutayeh ◽  
Asma Ismail Mahmod

Cancer is one of the main causes of death globally and considered as a major challenge for the public health system. The high toxicity and the lack of selectivity of conventional anticancer therapies make the search for alternative treatments a priority. In this review, we describe the main plant-derived natural products used as anticancer agents. Natural sources, extraction methods, anticancer mechanisms, clinical studies, and pharmaceutical formulation are discussed in this review. Studies covered by this review should provide a solid foundation for researchers and physicians to enhance basic and clinical research on developing alternative anticancer therapies.


Author(s):  
Patrick Videau ◽  
Kaitlyn Wells ◽  
Arun Singh ◽  
Jessie Eiting ◽  
Philip Proteau ◽  
...  

Cyanobacteria are prolific producers of natural products and genome mining has shown that many orphan biosynthetic gene clusters can be found in sequenced cyanobacterial genomes. New tools and methodologies are required to investigate these biosynthetic gene clusters and here we present the use of <i>Anabaena </i>sp. strain PCC 7120 as a host for combinatorial biosynthesis of natural products using the indolactam natural products (lyngbyatoxin A, pendolmycin, and teleocidin B-4) as a test case. We were able to successfully produce all three compounds using codon optimized genes from Actinobacteria. We also introduce a new plasmid backbone based on the native <i>Anabaena</i>7120 plasmid pCC7120ζ and show that production of teleocidin B-4 can be accomplished using a two-plasmid system, which can be introduced by co-conjugation.


Author(s):  
Jing Liu ◽  
Can Liu ◽  
Yonghai Rong ◽  
Long Rong

The extraction yields of mogroside from Siraitia grosvenorii fruits and limonin from orange (Citrus reticulata Blanco) seeds were compared with different extraction methods, respectively. Maceration extraction, stirring extraction, ultrasonic extraction and flash extraction were used for the extraction. The extraction process was modeled using the concept of thin film which provides the resistance to transfer. The results showed that the maximum yields of mogroside (4.11%) and limonin (0.65%) were obtained by ultrasonic extraction and flash extraction respectively. Owing to its shorter extraction time, flash extraction would be an economical method for the mass production of triterpenes from natural products. The model was found to be fit for the comparison of methods for the extraction and provided good correlation of the data. The model could be mainly used in the practical extraction process.


2021 ◽  
Vol 85 (1) ◽  
pp. 42-52
Author(s):  
Taro Shiraishi ◽  
Tomohisa Kuzuyama

Abstract Phosphonates are organophosphorus compounds possessing a characteristic C−P bond in which phosphorus is directly bonded to carbon. As phosphonates mimic the phosphates and carboxylates of biological molecules to potentially inhibit metabolic enzymes, they could be lead compounds for the development of a variety of drugs. Fosfomycin (FM) is a representative phosphonate natural product that is widely used as an antibacterial drug. Here, we review the biosynthesis of FM, which includes a recent breakthrough to find a missing link in the biosynthetic pathway that had been a mystery for a quarter-century. In addition, we describe the genome mining of phosphonate natural products using the biosynthetic gene encoding an enzyme that catalyzes C–P bond formation. We also introduce the chemoenzymatic synthesis of phosphonate derivatives. These studies expand the repertoires of phosphonates and the related biosynthetic machinery. This review mainly covers the years 2012-2020.


Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2542
Author(s):  
Linda Sukmarini

Natural products (NPs) are evolutionarily optimized as drug-like molecules and remain the most consistently successful source of drugs and drug leads. They offer major opportunities for finding novel lead structures that are active against a broad spectrum of assay targets, particularly those from secondary metabolites of microbial origin. Due to traditional discovery approaches’ limitations relying on untargeted screening methods, there is a growing trend to employ unconventional secondary metabolomics techniques. Aided by the more in-depth understanding of different biosynthetic pathways and the technological advancement in analytical instrumentation, the development of new methodologies provides an alternative that can accelerate discoveries of new lead-structures of natural origin. This present mini-review briefly discusses selected examples regarding advancements in bioinformatics and genomics (focusing on genome mining and metagenomics approaches), as well as bioanalytics (mass-spectrometry) towards the microbial NPs-based drug discovery and development. The selected recent discoveries from 2015 to 2020 are featured herein.


mSystems ◽  
2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Daniela B. B. Trivella ◽  
Rafael de Felicio

ABSTRACT Natural products are the richest source of chemical compounds for drug discovery. Particularly, bacterial secondary metabolites are in the spotlight due to advances in genome sequencing and mining, as well as for the potential of biosynthetic pathway manipulation to awake silent (cryptic) gene clusters under laboratory cultivation. Further progress in compound detection, such as the development of the tandem mass spectrometry (MS/MS) molecular networking approach, has contributed to the discovery of novel bacterial natural products. The latter can be applied directly to bacterial crude extracts for identifying and dereplicating known compounds, therefore assisting the prioritization of extracts containing novel natural products, for example. In our opinion, these three approaches—genome mining, silent pathway induction, and MS-based molecular networking—compose the tripod for modern bacterial natural product discovery and will be discussed in this perspective.


2021 ◽  
Vol 21 (17) ◽  
pp. 1517-1518
Author(s):  
Dharmendra Kumar Yadav

The discovery and utilization of novel metabolites from natural sources are gaining momentum in the present era. The drug discovery programs have witnessed a remarkable shift from conventional medicines to exploiting natural products and their “value addition”, for treating lifethreatening diseases. The global outbreak of life-threatening diseases namely Ebola, SARS,including infections of the bloodstream (bacteremia), heart valves (endocarditis), lungs (pneumonia), and brain (meningitis) and AIDS calls for a more targeted approach to effectively combat the emerging diseases. In the present scenario, natural products and their extracts are being explored extensively for the treatment of various life threatening diseases. In this thematic issue, several review articles contributed by the scientist and researchers in the different areas of medicinal chemistry, synthetic chemistry, new emerging multi-drug targets were collected. This issue begins with a review article on the “Chemistry and Pharmacology of Natural Catechins from Camellia sinensis as anti-MRSA agents” by Gaur et al. and focuses on the spread of MRSA strains is of great concern because of limited treatment options for staphylococcal infections, since these strains are resistant to the entire class of β-lactam antibiotics. In addition, MRSA exhibits resistance to other classes of antimicrobial agents such as fluoroquinolones, cephalosporins, aminoglycosides, macrolide and even glycopeptides (vancomycin and teicoplanine), leading to the emergence of resistant strains such as glycopeptide intermediate (GISA) and resistant strain (GRSA) of S. aureus. In this review, chemical constituents responsible for the anti-MRSA activity of tea are explored [1]. The next article of this issue is a review article on the “Recent Advancements in the Synthesis and Chemistry of Benzofused Nitrogen- and Oxygen-based Bioactive Heterocycles” by Sharma et al. which focuses on medicinal importance of these bioactive benzo-fused heterocycles; special attention has been given to their synthesis as well as medicinal/pharmaceutical properties in detail [2]. “Trends in pharmaceutical design of Endophytes as anti-infective,” by Tiwari et al., is the third article in this issue. The review focused on the meta-analysis of bioactive metabolite production from endophytes, extensively discussing the bioprospection of natural products for pharmaceutical applications. In light of the emerging importance of endophytes as antiinfective agents, an exploration of the pharmaceutical design of novel chemical entities and analogues has enabled efficient and cost-effective drug discovery programs. However, bottlenecks in endophytic biology and research requires a better understanding of endophytic dynamics and mechanism of bioactive metabolite production towards a sustainable drug discovery program [3]. The last article of this issue is also research article on “Recent development of tetrahydro-quinoline/isoquinoline based compounds as anticancer agents” by Yadav et al. The article reported the synthesis of potent tetrahydroquinoline/isoquinoline molecules of the last 10 years with their anticancer properties in various cancer cell lines and stated their half-maximal inhibitory concentration (IC50). In addition, we also considered the discussion of molecular docking and structural activity relationship wherever provided to understand the possible mode of activity an target involved and structural features responsible for the better activity, so the reader can directly find detail for designing new anticancer agents. [4]. Finally I would like to thank all authors who contributed to this issue, titled “Recent advances on small molecule medicinal chemistry to treat human diseases”.


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