scholarly journals Activation of cryptic metabolite production through gene disruption: Dimethyl furan-2,4-dicarboxylate produced by Streptomyces sahachiroi

2013 ◽  
Vol 9 ◽  
pp. 1768-1773 ◽  
Author(s):  
Dinesh Simkhada ◽  
Huitu Zhang ◽  
Shogo Mori ◽  
Howard Williams ◽  
Coran M H Watanabe
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Small Molecule ◽  
Related Compound ◽  
Gene Disruption ◽  
Genome Sequences ◽  
Bioactive Natural Products ◽  
Genetic Knockout ◽  
Small Molecule Drugs ◽  
Peptide Synthetase

At least 65% of all small molecule drugs on the market today are natural products, however, re-isolation of previously identified and characterized compounds has become a serious impediment to the discovery of new bioactive natural products. Here, genetic knockout of an unusual non-ribosomal peptide synthetase (NRPS) C-PCP-C module, aziA2, is performed resulting in the accumulation of the secondary metabolite, dimethyl furan-2,4-dicarboxylate. The cryptic metabolite represents the first non-azinomycin related compound to be isolated and characterized from the soil bacterium, S. sahachiroi. The results from this study suggest that abolishing production of otherwise predominant natural products through genetic knockout may constitute a means to “activate” the production of novel secondary metabolites that would otherwise lay dormant within microbial genome sequences.

scholarly journals A Review of Anti-Inflammatory Compounds from Marine Fungi, 2000–2018

Marine Drugs ◽  
2019 ◽  
Vol 17 (11) ◽  
pp. 636 ◽  
Author(s):  
Jianzhou Xu ◽  
Mengqi Yi ◽  
Lijian Ding ◽  
Shan He
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Host Response ◽  
Marine Fungi ◽  
Tissue Injury ◽  
Fungal Metabolites ◽  
Bioactive Natural Products ◽  
Anti Inflammatory ◽  
Unique Mechanism ◽  
Inflammatory Action

Inflammation is a generalized, nonspecific, and beneficial host response of foreign challenge or tissue injury. However, prolonged inflammation is undesirable. It will cause loss function of involve organs, such as heat, pain redness, and swelling. Marine natural products have gained more and more attention due to their unique mechanism of anti-inflammatory action, and have considered a hotspot for anti-inflammatory drug development. Marine-derived fungi are promising sources of structurally unprecedented bioactive natural products. So far, a plethora of new secondary metabolites with anti-inflammatory activities from marine-derived fungi had been widely reported. This review covers 133 fungal metabolites described in the period of 2000 to 2018, including the structures and origins of these secondary metabolites.

scholarly journals New and bioactive natural products from an endophyte of Panax notoginseng

RSC Advances ◽  
2017 ◽  
Vol 7 (60) ◽  
pp. 38100-38109 ◽  
Author(s):  
Jun Xie ◽  
Ying-Ying Wu ◽  
Tian-Yuan Zhang ◽  
Meng-Yue Zhang ◽  
Wei-Wei Zhu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Natural Products ◽  
Secondary Metabolites ◽  
Antiviral Activity ◽  
Cytotoxic Activity ◽  
Endophytic Fungi ◽  
Panax Notoginseng ◽  
Bioactive Natural Products

Secondary metabolites with cytotoxic activity, antiviral activity and antimicrobial activity from the endophytic fungi of Panax notoginseng.

Bioprospecting microbial metagenome for natural products

Biologia ◽  
2013 ◽  
Vol 68 (6) ◽  
Author(s):  
Jana Nováková ◽  
Marián Farkašovský
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Secondary Metabolites ◽  
Functional Diversity ◽  
Genetic Information ◽  
Microbial World ◽  
Future Directions ◽  
Natural Sources ◽  
Bioactive Natural Products ◽  
Uncultured Bacteria

AbstractMining of natural sources for new secondary metabolites has a successful history, which is reflected by the fact that over 50% of all drugs, currently on the market, are derived from natural products. Bacteria are one of the most important sources of bioactive natural products destined for drug discovery. However, less than 1% of the microorganisms observed in different habitats have been cultivated and characterized. To explore the genomic and functional diversity of the vast majority of the microbial world, novel methods were introduced, which are based on analysis of a DNA isolated from environmental communities. Metagenomics represents a strategy offering access to the genetic information present in uncultured bacteria by screening of libraries constructed from DNA isolated from different habitats. Functional- and sequence-driven screens are the major approaches employed to mine metagenomic libraries. This review aims to highlight discoveries in this area and discusses the possible future directions of the field.

scholarly journals Targeting Autophagy with Natural Compounds in Cancer: A Renewed Perspective from Molecular Mechanisms to Targeted Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiang Xie ◽  
Yi Chen ◽  
Huidan Tan ◽  
Bo Liu ◽  
Ling-Li Zheng ◽  
...  
Keyword(s):  
Natural Products ◽  
Cancer Therapy ◽  
Signaling Pathways ◽  
Small Molecule ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Natural Compounds ◽  
Therapeutic Effects ◽  
Therapeutic Benefits ◽  
Small Molecule Drugs

Natural products are well-characterized to have pharmacological or biological activities that can be of therapeutic benefits for cancer therapy, which also provide an important source of inspiration for discovery of potential novel small-molecule drugs. In the past three decades, accumulating evidence has revealed that natural products can modulate a series of key autophagic signaling pathways and display therapeutic effects in different types of human cancers. In this review, we focus on summarizing some representative natural active compounds, mainly including curcumin, resveratrol, paclitaxel, Bufalin, and Ursolic acid that may ultimately trigger cancer cell death through the regulation of some key autophagic signaling pathways, such as RAS-RAF-MEK-ERK, PI3K-AKT-mTOR, AMPK, ULK1, Beclin-1, Atg5 and p53. Taken together, these inspiring findings would shed light on exploiting more natural compounds as candidate small-molecule drugs, by targeting the crucial pathways of autophagy for the future cancer therapy.

Research progress on secondary metabolites from the ascidians of Aplidium genus

2020 ◽  
Vol 17 ◽  
Author(s):  
Qing-Hua Han ◽  
Xiao-Qing Tian ◽  
Shu-Ming Zhao ◽  
Ya-Nan Lu ◽  
Cheng-Qi Fan
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Marine Environment ◽  
Chemical Diversity ◽  
Research Progress ◽  
China Seas ◽  
Bioactive Natural Products ◽  
The Family ◽  
Further Development

Abstract: Ascidians (tunicates) are widely recognized as one of the most prolific producers of bioactive natural products in the marine environment. This present study reviewed the chemical diversity of marine ascidians from the Aplidium genus and their pharmacological applications since Jan 2005. The resources of this genus from China Seas, including the changes of their names in the family Polydinidae were also summarized in this paper. In addition, a concise outlook on their chemi-cal and pharmaceutical investigation is made to support further development

scholarly journals Marine Rare Actinomycetes: A Promising Source of Structurally Diverse and Unique Novel Natural Products

Marine Drugs ◽  
2019 ◽  
Vol 17 (5) ◽  
pp. 249 ◽  
Author(s):  
Subramani ◽  
Sipkema
Keyword(s):  
Natural Products ◽  
New Species ◽  
Secondary Metabolites ◽  
Natural Product ◽  
Bioactive Compounds ◽  
Marine Environment ◽  
Present Knowledge ◽  
Bioactive Natural Products ◽  
Rare Actinomycetes ◽  
Promising Source

Rare actinomycetes are prolific in the marine environment; however, knowledge about their diversity, distribution and biochemistry is limited. Marine rare actinomycetes represent a rather untapped source of chemically diverse secondary metabolites and novel bioactive compounds. In this review, we aim to summarize the present knowledge on the isolation, diversity, distribution and natural product discovery of marine rare actinomycetes reported from mid-2013 to 2017. A total of 97 new species, representing 9 novel genera and belonging to 27 families of marine rare actinomycetes have been reported, with the highest numbers of novel isolates from the families Pseudonocardiaceae, Demequinaceae, Micromonosporaceae and Nocardioidaceae. Additionally, this study reviewed 167 new bioactive compounds produced by 58 different rare actinomycete species representing 24 genera. Most of the compounds produced by the marine rare actinomycetes present antibacterial, antifungal, antiparasitic, anticancer or antimalarial activities. The highest numbers of natural products were derived from the genera Nocardiopsis, Micromonospora, Salinispora and Pseudonocardia. Members of the genus Micromonospora were revealed to be the richest source of chemically diverse and unique bioactive natural products.

scholarly journals Metabolites from marine invertebrates and their symbiotic microorganisms: molecular diversity discovery, mining, and application

2019 ◽  
Vol 1 (1) ◽  
pp. 60-94 ◽  
Author(s):  
Lu Liu ◽  
Yao-Yao Zheng ◽  
Chang-Lun Shao ◽  
Chang-Yun Wang
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Molecular Diversity ◽  
Marine Invertebrates ◽  
Epigenetic Modification ◽  
Marine Organisms ◽  
Bioactive Molecules ◽  
Bioactive Natural Products ◽  
Symbiotic Microorganisms ◽  
Symbiotic Fungi

Abstract Metabolites from marine organisms have proven to be a rich source for the discovery of multiple potent bioactive molecules with diverse structures. In recent years, we initiated a program to investigate the diversity of the secondary metabolites from marine invertebrates and their symbiotic microorganisms collected from the South China Sea. In this review, representative cases are summarized focusing on molecular diversity, mining, and application of natural products from these marine organisms. To provide a comprehensive introduction to the field of marine natural products, we highlight typical molecules including their structures, chemical synthesis, bioactivities and mechanisms, structure–activity relationships as well as biogenesis. The mining of marine-derived microorganisms to produce novel secondary metabolites is also discussed through the OSMAC strategy and via partial chemical epigenetic modification. A broad prospectus has revealed a plethora of bioactive natural products with novel structures from marine organisms, especially from soft corals, gorgonians, sponges, and their symbiotic fungi and bacteria.

scholarly journals Bioactive natural products from fungicolous Hawaiian isolates: secondary metabolites from aPhialemoniopsissp.

2014 ◽  
Vol 5 (3) ◽  
pp. 120-129 ◽  
Author(s):  
Amninder Kaur ◽  
Kristina D. Rogers ◽  
Dale E. Swenson ◽  
Patrick F. Dowd ◽  
Donald T. Wicklow ◽  
...  
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Bioactive Natural Products

scholarly journals Catalytic Use of a Leader Peptide in the Biosynthesis of 3-Thiaglutamate

2018 ◽  
Author(s):  
Michael A. Funk ◽  
Chi Ting ◽  
Wilfred A. van der Donk
Keyword(s):  
Natural Products ◽  
Pseudomonas Syringae ◽  
Small Molecule ◽  
Cysteine Residue ◽  
Leader Peptide ◽  
Genome Sequences ◽  
Small Peptide ◽  
Biochemical Processes ◽  
C Terminus ◽  
Ribosomal Protein Synthesis

AbstractSmall molecule natural products are key modulators of many types of intra- and interspecies communication. The availability of genome sequences allows the discovery of pathways to previously unknown natural products. We describe here a pathway in which a ribosomally synthesized small peptide serves as a catalytic scaffold on which a small-molecule anti-metabolite is biosynthesized in Pseudomonas syringae. First, a cysteine residue is transferred from Cys-tRNA to the C-terminus of the peptide, a reaction that replaces ribosomal protein synthesis. Then, a translocation of the cysteine thiol from the β-carbon to the α-carbon is catalyzed by an oxidase that removes the β-carbon as formate. The resulting thiol is carboxymethylated and proteolysis releases 3-thiaglutamate, in the process regenerating the peptide scaffold. This pathway features three previously unknown biochemical processes.

scholarly journals High-Resolution MS, MS/MS, and UV Database of Fungal Secondary Metabolites as a Dereplication Protocol for Bioactive Natural Products

2013 ◽  
Vol 76 (9) ◽  
pp. 1709-1716 ◽  
Author(s):  
Tamam El-Elimat ◽  
Mario Figueroa ◽  
Brandie M. Ehrmann ◽  
Nadja B. Cech ◽  
Cedric J. Pearce ◽  
...  
Keyword(s):  
Natural Products ◽  
High Resolution ◽  
Secondary Metabolites ◽  
Bioactive Natural Products ◽  
Fungal Secondary Metabolites
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