Genomics-guided discovery of potent anticancer natural products from exotic bacterial species

Planta Medica ◽  
2014 ◽  
Vol 80 (10) ◽  
Author(s):  
YQE Cheng
Keyword(s):  
Natural Products ◽  
Bacterial Species ◽  
Guided Discovery

scholarly journals Inflammation, HIV, and Immune Quiescence: Leveraging on Immunomodulatory Products to Reduce HIV Susceptibility

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Ross Cromarty ◽  
Derseree Archary
Keyword(s):  
Natural Products ◽  
Disease Progression ◽  
Hiv Risk ◽  
Immune Activation ◽  
Bacterial Species ◽  
Lactobacillus Species ◽  
Immune Correlates ◽  
Immune Quiescence ◽  
Anti Inflammatory ◽  
Reduced Risk

The relationship between inflammation and HIV has been a focus of research over the last decade. In HIV-infected individuals, increased HIV-associated immune activation significantly correlated to disease progression. While genital inflammation (GI) has been shown to significantly increase the risk of HIV acquisition and transmission, immune correlates for reduced risk remain limited. In certain HIV-exposed seronegative individuals, an immune quiescent phenotype characterized reduced risk. Immune quiescence is defined by specific, targeted, highly regulated immune responses that hinder overt inflammation or immune activation. Targeted management of inflammation, therefore, is a plausible strategy to mitigate HIV risk and slow disease progression. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as hydroxychloroquine and aspirin have shown encouraging preliminary results in low-risk women by reducing systemic and genital immune activation. A topical NSAID, containing ibuprofen, is effective in treating vulvovaginal inflammation. Additionally, the glucocorticoids (GCs), prednisolone, and dexamethasone are used to treat HIV-associated immune activation. Collectively, these data inform on immune-modulating drugs to reduce HIV risk. However, the prolonged use of these pharmaceutical drugs is associated with adverse effects, both systemically and to a lesser extent topically. Natural products with their reduced side effects coupled with anti-inflammatory properties render them viable options. Lactic acid (LA) has immunomodulatory properties. LA regulates the genital microbiome by facilitating the growth of Lactobacillus species, while simultaneously limiting bacterial species that cause microbial dysbiosis and GI. Glycerol monolaurate, besides being anti-inflammatory, also inhibited SIV infections in rhesus macaques. The proposed pharmaceutical and natural products could be used in combination with either antiretrovirals for treatment or preexposure prophylaxis for HIV prevention. This review provides a summary on the associations between inflammation, HIV risk, and disease progression. Furthermore, we use the knowledge from immune quiescence to exploit the use of pharmaceutical and natural products as strategic interventions to manage inflammation, toward mitigating HIV infections.

scholarly journals Ribosomally derived lipopeptides containing distinct fatty acyl moieties

2022 ◽  
Vol 119 (3) ◽  
pp. e2113120119
Author(s):  
Florian Hubrich ◽  
Nina M. Bösch ◽  
Clara Chepkirui ◽  
Brandon I. Morinaka ◽  
Michael Rust ◽  
...  
Keyword(s):  
Natural Products ◽  
Cyclic Peptide ◽  
Fatty Acyl ◽  
Antifungal Drugs ◽  
Guided Discovery ◽  
Bacterial Phyla ◽  
Peptide Synthetases ◽  
Antibacterial And Antifungal ◽  
Microbial Natural Products

Lipopeptides represent a large group of microbial natural products that include important antibacterial and antifungal drugs and some of the most-powerful known biosurfactants. The vast majority of lipopeptides comprise cyclic peptide backbones N-terminally equipped with various fatty acyl moieties. The known compounds of this type are biosynthesized by nonribosomal peptide synthetases, giant enzyme complexes that assemble their products in a non–gene-encoded manner. Here, we report the genome-guided discovery of ribosomally derived, fatty-acylated lipopeptides, termed selidamides. Heterologous reconstitution of three pathways, two from cyanobacteria and one from an arctic, ocean-derived alphaproteobacterium, allowed structural characterization of the probable natural products and suggest that selidamides are widespread over various bacterial phyla. The identified representatives feature cyclic peptide moieties and fatty acyl units attached to (hydroxy)ornithine or lysine side chains by maturases of the GCN5-related N-acetyltransferase superfamily. In contrast to nonribosomal lipopeptides that are usually produced as congener mixtures, the three selidamides are selectively fatty acylated with C10, C12, or C16 fatty acids, respectively. These results highlight the ability of ribosomal pathways to emulate products with diverse, nonribosomal-like features and add to the biocatalytic toolbox for peptide drug improvement and targeted discovery.

scholarly journals Microbially guided discovery and biosynthesis of biologically active natural products

2021 ◽  
Author(s):  
Ankur Sarkar ◽  
Edward Kim ◽  
Taehwan Jang ◽  
Akarawin Hongdusit ◽  
Hyungjun Kim ◽  
...  
Keyword(s):  
Natural Products ◽  
Tyrosine Phosphatase ◽  
Biologically Active ◽  
Allosteric Site ◽  
Terpene Synthases ◽  
Guided Discovery ◽  
Detection Systems ◽  
Treatment Of Diabetes ◽  
Active Natural ◽  
Microbial Host

Abstract The design of small molecules that inhibit disease-relevant proteins represents a longstanding challenge of medicinal chemistry. Here, we describe an approach for encoding this challenge—the inhibition of a human drug target—into a microbial host and using it to guide the discovery and biosynthesis of targeted, biologically active natural products. This approach identified two previously unknown terpenoid inhibitors of protein tyrosine phosphatase 1B (PTP1B), an elusive therapeutic target for the treatment of diabetes and cancer. Both inhibitors appear to target an allosteric site, which confers selectivity, and can inhibit PTP1B in living cells. A screen of 24 uncharacterized terpene synthases from a pool of 4,464 genes uncovered additional hits, demonstrating a scalable discovery approach, and the incorporation of different PTPs into the microbial host yielded alternative PTP-specific detection systems. Findings illustrate the potential for using microbes to discover and build natural products that exhibit precisely defined biochemical activities yet possess unanticipated structures and/or binding sites.

INVITRO EVALUATION OF ANTIMICROBIAL ACTIVITY OF CLOVE BUDS( EUGINEA AROMATICA)

2020 ◽  
pp. 25-33
Author(s):  
A.Mounika A.Mounika ◽  
M.Sushma M.Sushma ◽  
Lahari Sidde Lahari Sidde ◽  
Sankara Malathi Sankara Malathi ◽  
Konapalli Rajani Konapalli Rajani
Keyword(s):  
Antimicrobial Activity ◽  
Natural Products ◽  
Bacterial Species ◽  
Antimicrobial Activities ◽  
Diffusion Method ◽  
Screening Methods ◽  
Clove Oil ◽  
Agar Diffusion ◽  
Variant Method ◽  
Varied Range

Bioactive compounds from Eugenia  aromaticum were extracted by Soxhlet using DCM ,DCM;WATER,WATER and extracts were examined for its phytocomponents along with Clove oil. These bioactive plant compounds were screened for possible antimicrobial activities against two strains of MDR S. aureus. Antimicrobial activity of extracts using agar diffusion disc variant  method. The objective of this study was to evaluate technical variants used in screening methods to determine antibacterial activity of natural products. Thus, a varied range of natural products of plant were tested against two bacterial species,m Staphylococcus aureus ATCC 25923 and klebesella pnemonia ATCC 25922, by two variants of the agar diffusion method (well and disc), two variants of the bio autographic method (direct and indirect) and by microdilution assay. We concluded that the well-variant of the diffusion method was more sensitive than the disc-variant,  it was found extract 1 ie,DCM  and extract 2 i.e DCM;WATER had shown best results on antimicrobial activity ,phytocvhemical screening test are done for three extractsn invitro evalvation of antimicrobial activity was performed.

Genome-Guided Discovery of Natural Products and Biosynthetic Pathways from Australia’s Untapped Microbial Megadiversity

2016 ◽  
Vol 69 (2) ◽  
pp. 129 ◽  
Author(s):  
John A. Kalaitzis ◽  
Shane D. Ingrey ◽  
Rocky Chau ◽  
Yvette Simon ◽  
Brett A. Neilan
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Genome Sequencing ◽  
Dna Sequences ◽  
Gene Clusters ◽  
Biosynthetic Pathways ◽  
Natural Product Biosynthesis ◽  
Guided Discovery ◽  
Biosynthesis Gene ◽  
Microbial Natural Products

Historically microbial natural product biosynthesis pathways were elucidated mainly by isotope labelled precursor directed feeding studies. Now the genetics underpinning the assembly of microbial natural products biosynthesis is so well understood that some pathways and their products can be predicted from DNA sequences alone. The association between microbial natural products and their biosynthesis gene clusters is now driving the field of ‘genetics guided natural product discovery’. This account overviews our research into cyanotoxin biosynthesis before the genome sequencing era through to some recent discoveries resulting from the mining of Australian biota for natural product biosynthesis pathways.

scholarly journals Direct Capture Technologies for Genomics-Guided Discovery of Natural Products

2016 ◽  
Vol 16 (15) ◽  
pp. 1695-1704 ◽  
Author(s):  
Andrew N. Chan ◽  
Kevin C. Santa Maria ◽  
Bo Li
Keyword(s):  
Natural Products ◽  
Guided Discovery ◽  
Direct Capture

scholarly journals Public questions spur the discovery of new bacterial species associated with lignin bioconversion of industrial waste

2019 ◽  
Vol 6 (3) ◽  
pp. 180748 ◽  
Author(s):  
Stephanie L. Mathews ◽  
Mary Jane Epps ◽  
R. Kevin Blackburn ◽  
Michael B. Goshe ◽  
Amy M. Grunden ◽  
...  
Keyword(s):  
Industrial Waste ◽  
Bacterial Species ◽  
Black Liquor ◽  
Waste Product ◽  
Value Added ◽  
Bacterial Strains ◽  
Guided Discovery ◽  
Public Response ◽  
Degrading Bacteria ◽  
Citizen Science Project

A citizen science project found that the greenhouse camel cricket ( Diestrammena asynamora ) is common in North American homes. Public response was to wonder ‘what good are they anyway?’ and ecology and evolution guided the search for potential benefit. We predicted that camel crickets and similar household species would likely host bacteria with the ability to degrade recalcitrant carbon compounds. Lignocellulose is particularly relevant as it is difficult to degrade yet is an important feedstock for pulp and paper, chemical and biofuel industries. We screened gut bacteria of greenhouse camel crickets and another household insect, the hide beetle ( Dermestes maculatus ) for the ability to grow on and degrade lignocellulose components as well as the lignocellulose-derived industrial waste product black liquor. From three greenhouse camel crickets and three hide beetles, 14 bacterial strains were identified that were capable of growth on lignocellulosic components, including lignin. Cedecea lapagei was selected for further study due to growth on most lignocellulose components. The C. lapagei secretome was identified using LC/MS/MS analysis. This work demonstrates a novel source of lignocellulose-degrading bacteria and introduces an effective workflow to identify bacterial enzymes for transforming industrial waste into value-added products. More generally, our research suggests the value of ecologically guided discovery of novel organisms.

Data Resources for the Computer-Guided Discovery of Bioactive Natural Products

2017 ◽  
Vol 57 (9) ◽  
pp. 2099-2111 ◽  
Author(s):  
Ya Chen ◽  
Christina de Bruyn Kops ◽  
Johannes Kirchmair
Keyword(s):  
Natural Products ◽  
Guided Discovery ◽  
Bioactive Natural Products

scholarly journals Gene Cluster Analysis of Marine Bacteria Seeking for Natural Anticancer Products

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Ashraf Mohamadkhani
Keyword(s):  
Natural Products ◽  
Marine Bacteria ◽  
Chemical Engineering ◽  
Biological Activities ◽  
Bacterial Species ◽  
Bacterial Genome ◽  
Gene Clusters ◽  
Marine Microorganisms ◽  
Genome Database ◽  
Anti Cancer

Background: In the past decade, metabolites of marine microorganisms have been increasingly used for their various biological activities. An intense effort has been dedicated to assessing the therapeutic efficacy of the marine natural products and metabolites obtained from marine bacteria in cancer therapy. Fast and reliable analytical bacterial genome sequencing provides specialized bioinformatic tools to identify potential gene clusters in bacteria for obtaining secondary metabolites. Objectives: This study aimed to analyze the genome sequences of marine bacteria to recognize bioactive compounds with anti-cancer properties. Methods: Marine bacteria with the genomic sequences registered in the National Center for Biotechnology Information (NCBI) genome database were used in this study. The genome was analyzed for proteins, tRNAs, and rRNAs from GenBank entries by Feature Extract 1.2L Server. The Anti-SMASH webserver was used for the analysis of unique marine bacterial metabolites of the marine bacterial genome, available from the NCBI database. Results: A number of marine bacterial species, including Salinispora arenicola, Salinispora tropica, Crocosphaera watsonii, and Blastopirellula marina encoded metabolites belonging to the polyketide and nonribosomal peptide (NRP) families, showing anti-cancer properties. Among the marine species described, S. tropica and S. arenicola are richer in the genes encoding polyketide and NRP with potential antitumor activities. Conclusions: Marine bacteria are an excellent and exceptional source of anti-cancer compounds. In silico genome analysis of marine bacteria provided an opportunity to evaluate gene clusters for known natural products. Like this chemical engineering approaches for pharmaceutical application are useful in clinical evaluation of cancer treatment.

scholarly journals Understanding the evolutionary origins of bacterial natural products with immunosuppressant properties

2019 ◽  
Author(s):  
Wenfa Ng
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Human Body ◽  
Immune Cells ◽  
Bacterial Species ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Drug Candidates

Actinobacteria and streptomyces are known to produce a variety of natural products, some of which confer antibiotic or immunosuppressive activities. While it is understandable that microbes develop the ability to synthesize molecules such as antibiotics that attack other competing microbes, but why would a secondary metabolite (natural product) synthesized by a microbe confer immunosuppressive activities? Was the capability to synthesize such a molecule endowed by evolution in the context of enabling microbes to develop resistance to immune cells of the human body? Or did the capability come from the need to colonize human body surfaces or gut to gain a survival niche for the microbe? Given that actinobacteria and streptomyces are soil microbes not usually associated with human body surfaces, could their biosynthetic capability for particular immunosuppressants arise from horizontal gene transfer from bacteria that colonize human body surfaces and subsequently develop the ability to synthesize the pertinent compounds through evolution? An alternate line of thinking on this issue touches on the possibility that microbes could encounter analogs of immuno-active molecules in their natural environment. Such molecules might elicit undesired physiological effects on the microbes, which place a selection pressure on microbes to develop countermeasures to the immuno-active molecules through mutations. Hence, through evolution, microbes could have developed the capability to synthesize secondary metabolites able to bind analogs of immuno-active molecules and help sequester them or quench their bioactivity. Subsequent profiling of such secondary metabolites in drug discovery efforts could have uncovered compounds with immunosuppressant activity which are originally developed for counteracting analogs of immuno-active molecules in the environment. It has to be recognized that analogs of immuno-active compounds remain somewhat dissimilar to immune compounds secreted by human immune cells, but they likely share common motifs for protein-secondary metabolite interactions. Direct evidence of the evolution of natural products with immunosuppressant activities could only be obtained from challenging suitable bacterial species with immuno-active molecules. Long cultivation experiments with multiple generations may result in the evolution of biosynthetic gene clusters for the synthesis of natural products able to sequester or quench immuno-active molecules. But, on the another hand, understanding relative binding affinities between a library of natural products and immuno-active molecules from humans would suggest drug candidates and their biosynthetic gene clusters. Subsequent phylogenetic analysis of cluster genes with their homologs from other species may yield insights into the evolution of genes and their putative function.

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