scholarly journals Biosynthesis of C-nucleoside antibiotics in actinobacteria: recent advances and future developments

2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Meng Zhang ◽  
Liyuan Kong ◽  
Rong Gong ◽  
Marianna Iorio ◽  
Stefano Donadio ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Synthetic Biology ◽  
Plant Protection ◽  
Biological Activities ◽  
Genome Mining ◽  
Nucleoside Antibiotics ◽  
Future Developments ◽  
Recent Advances ◽  
Microbial Natural Products ◽  
Epidemic Diseases

AbstractEpidemic diseases and antibiotic resistance are urgent threats to global health, and human is confronted with an unprecedented dilemma to conquer them by expediting development of new natural product related drugs. C-nucleoside antibiotics, a remarkable group of microbial natural products with diverse biological activities, feature a heterocycle base linked with a ribosyl moiety via an unusual C-glycosidic bond, and have played significant roles in healthcare and for plant protection. Elucidating how nature biosynthesizes such a group of antibiotics has provided the basis for engineered biosynthesis as well as targeted genome mining of more C-nucleoside antibiotics towards improved properties. In this review, we mainly summarize the recent advances on the biosynthesis of C-nucleoside antibiotics, and we also tentatively discuss the future developments on rationally accessing C-nucleoside diversities in a more efficient and economical way via synthetic biology strategies.

scholarly journals Comparative Investigation into Formycin A and Pyrazofurin A Biosynthesis Reveals Branch Pathways for the Construction of C-Nucleoside Scaffolds

2019 ◽  
Vol 86 (2) ◽  
Author(s):  
Meng Zhang ◽  
Peichao Zhang ◽  
Gudan Xu ◽  
Wenting Zhou ◽  
Yaojie Gao ◽  
...  
Keyword(s):  
Biological Activities ◽  
Genome Mining ◽  
Gene Clusters ◽  
Combinatorial Biosynthesis ◽  
Glycosidic Bond ◽  
Enzymatic Reactions ◽  
Nucleoside Antibiotics ◽  
Enzymatic Mechanism ◽  
Chemical Structures ◽  
The Way

ABSTRACT Formycin A (FOR-A) and pyrazofurin A (PRF-A) are purine-related C-nucleoside antibiotics in which ribose and a pyrazole-derived base are linked by a C-glycosidic bond. However, the logic underlying the biosynthesis of these molecules has remained largely unexplored. Here, we report the discovery of the pathways for FOR-A and PRF-A biosynthesis from diverse actinobacteria and propose that their biosynthesis is likely initiated by a lysine N6-monooxygenase. Moreover, we show that forT and prfT (involved in FOR-A and PRF-A biosynthesis, respectively) mutants are correspondingly capable of accumulating the unexpected pyrazole-related intermediates 4-amino-3,5-dicarboxypyrazole and 3,5-dicarboxy-4-oxo-4,5-dihydropyrazole. We also decipher the enzymatic mechanism of ForT/PrfT for C-glycosidic bond formation in FOR-A/PRF-A biosynthesis. To our knowledge, ForT/PrfT represents an example of β-RFA-P (β-ribofuranosyl-aminobenzene 5ʹ-phosphate) synthase-like enzymes governing C-nucleoside scaffold construction in natural product biosynthesis. These data establish a foundation for combinatorial biosynthesis of related purine nucleoside antibiotics and also open the way for target-directed genome mining of PRF-A/FOR-A-related antibiotics. IMPORTANCE FOR-A and PRF-A are C-nucleoside antibiotics known for their unusual chemical structures and remarkable biological activities. Deciphering the enzymatic mechanism for the construction of a C-nucleoside scaffold during FOR-A/PRF-A biosynthesis will not only expand the biochemical repertoire for novel enzymatic reactions but also permit target-oriented genome mining of FOR-A/PRF-A-related C-nucleoside antibiotics. Moreover, the availability of FOR-A/PRF-A biosynthetic gene clusters will pave the way for the rational generation of designer FOR-A/PRF-A derivatives with enhanced/selective bioactivity via synthetic biology strategies.

scholarly journals Comparative investigation into formycin A and pyrazofurin A biosynthesis reveals branch pathways for the construction of C-nucleoside scaffolds

2019 ◽  
Author(s):  
Meng Zhang ◽  
Peichao Zhang ◽  
Gudan Xu ◽  
Wenting Zhou ◽  
Yaojie Gao ◽  
...  
Keyword(s):  
Biological Activities ◽  
Bond Formation ◽  
Genome Mining ◽  
Comparative Investigation ◽  
Combinatorial Biosynthesis ◽  
Glycosidic Bond ◽  
Enzymatic Reactions ◽  
Natural Product Biosynthesis ◽  
Nucleoside Antibiotics ◽  
Chemical Structures

ABSTRACTFormycin A (FOR-A) and pyrazofurin A (PRF-A) are purine-related C-nucleoside antibiotics, in which ribose and a pyrazole-derived base are linked by a C-glycosidic bond, however, the logic underlying the biosynthesis of these molecules has remained largely unexplored. Here, we report the discovery of the pathways for FOR-A and PRF-A biosynthesis from diverse actinobacteria, and demonstrate that their biosynthesis is initiated by a lysine N6-monooxygenase. Moreover, we show that the forT and prfE (individually related to FOR-A and PRF-A biosynthesis) mutants are correspondingly capable of accumulating the unexpected pyrazole-related intermediates, compound 11 and 9a. We also decipher the enzymatic basis of ForT/PrfE for the C-glycosidic bond formation in FOR-A/PRF-A biosynthesis. To our knowledge, ForT/PrfE represents the first example of β-RFA-P (β-ribofuranosyl-aminobenzene 5’-phosphate) synthase-like enzymes governing C-nucleoside scaffold construction in natural product biosynthesis. These data establish a foundation for combinatorial biosynthesis of related purine nucleoside antibiotics, and also open the way for target-directed genome mining of PRF-A/FOR-A related antibiotics.IMPORTANCEFormycin A (FOR-A) and pyrazofurin A (PRF-A) are well known for their unusual chemical structures and remarkable biological activities. Actually, deciphering FOR-A/PRF-A biosynthesis will not only expand biochemical repertoire for novel enzymatic reactions, but also permit the target-oriented genome mining of FOR-A/PRF-A related C-nucleoside antibiotics.

Recent Advances in Discovery, Biosynthesis and Genome Mining of Medicinally Relevant Polycyclic Tetramate Macrolactams

2016 ◽  
Vol 16 (15) ◽  
pp. 1727-1739 ◽  
Author(s):  
Guangtao Zhang ◽  
Wenjun Zhang ◽  
Subhasish Saha ◽  
Changsheng Zhang
Keyword(s):  
Genome Mining ◽  
Recent Advances

Synthetic Strategies, Chemical Reactivities and Biological Activities of 3-Thioxo-1,2,4-Triazin-5-Ones and Their Derivatives

2019 ◽  
Vol 16 (4) ◽  
pp. 308-322
Author(s):  
Mohammad S.T. Makki ◽  
Reda M. Abdel-Rahman ◽  
Abdulrahman S. Alharbi
Keyword(s):  
Biological Activities ◽  
Biological Evaluation ◽  
Literature Survey ◽  
Recent Advances ◽  
Nucleophilic Reagents ◽  
Anti Hiv ◽  
Biological Field

In recent years, a very interest in the synthesis of functionalized 3-thioxo-1,2,4-triazin-5- ones and their derivatives as vital probes has been increased, due to the important, applications of the medicinal, pharmacological, and biological field as a drug, semi drug, and bioactive systems. The present work review outlines extensive recent advances literature survey on the synthesis of sulfurbearing 1,2,4-triazin-5-one derivatives has been reconsidered. Also, the behavior of these family towards electrophilic and nucleophilic reagents in different media and conditions reported. The biological evaluation of the most synthesized systems included anticancer, anti-HIV, antimicrobial as well as their enzymatic effects (cellobiase produced by fungi) have been reported. The reactivity of these systems depends on the polarity of solvent, temperature, molarity as well as a type of tautomeric present.

scholarly journals Applications, challenges, and needs for employing synthetic biology beyond the lab

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sierra M. Brooks ◽  
Hal S. Alper
Keyword(s):  
Synthetic Biology ◽  
Great Promise ◽  
Long Term Storage ◽  
Autonomous Function ◽  
Recent Advances ◽  
Resource Limited ◽  
Major Application ◽  
Further Development ◽  
Probiotic Delivery

AbstractSynthetic biology holds great promise for addressing global needs. However, most current developments are not immediately translatable to ‘outside-the-lab’ scenarios that differ from controlled laboratory settings. Challenges include enabling long-term storage stability as well as operating in resource-limited and off-the-grid scenarios using autonomous function. Here we analyze recent advances in developing synthetic biological platforms for outside-the-lab scenarios with a focus on three major application spaces: bioproduction, biosensing, and closed-loop therapeutic and probiotic delivery. Across the Perspective, we highlight recent advances, areas for further development, possibilities for future applications, and the needs for innovation at the interface of other disciplines.

scholarly journals Metabolomic Analysis of The Chemical Diversity of South Africa Leaf Litter Fungal Species Using an Epigenetic Culture-Based Approach

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4262
Author(s):  
Rachel Serrano ◽  
Víctor González-Menéndez ◽  
Germán Martínez ◽  
Clara Toro ◽  
Jesús Martín ◽  
...  
Keyword(s):  
South Africa ◽  
Genome Mining ◽  
Fungal Species ◽  
Chemical Diversity ◽  
Fermentation Conditions ◽  
Metabolite Profiles ◽  
Different Populations ◽  
Fungal Genomes ◽  
Microbial Natural Products ◽  
Fermentation Media

Microbial natural products are an invaluable resource for the biotechnological industry. Genome mining studies have highlighted the huge biosynthetic potential of fungi, which is underexploited by standard fermentation conditions. Epigenetic effectors and/or cultivation-based approaches have successfully been applied to activate cryptic biosynthetic pathways in order to produce the chemical diversity suggested in available fungal genomes. The addition of Suberoylanilide Hydroxamic Acid to fermentation processes was evaluated to assess its effect on the metabolomic diversity of a taxonomically diverse fungal population. Here, metabolomic methodologies were implemented to identify changes in secondary metabolite profiles to determine the best fermentation conditions. The results confirmed previously described effects of the epigenetic modifier on the metabolism of a population of 232 wide diverse South Africa fungal strains cultured in different fermentation media where the induction of differential metabolites was observed. Furthermore, one solid-state fermentation (BRFT medium), two classic successful liquid fermentation media (LSFM and YES) and two new liquid media formulations (MCKX and SMK-II) were compared to identify the most productive conditions for the different populations of taxonomic subgroups.

Biosynthesis and synthetic biology of psychoactive natural products

2021 ◽  
Author(s):  
Cooper S. Jamieson ◽  
Joshua Misa ◽  
Yi Tang ◽  
John M. Billingsley
Keyword(s):  
Natural Products ◽  
Synthetic Biology ◽  
Biological Activities ◽  
Engineering Applications ◽  
Pathway Discovery

The biosynthetic logic employed by Nature in the construction of psychoactive natural products is reviewed, in addition to biological activities, methodologies enabling pathway discovery, and engineering applications.

scholarly journals Ocimum campechianum Mill. from Amazonian Ecuador: Chemical Composition and Biological Activities of Extracts and Their Main Constituents (Eugenol and Rosmarinic Acid)

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 84
Author(s):  
Massimo Tacchini ◽  
Monica Paulina Echeverria Guevara ◽  
Alessandro Grandini ◽  
Immacolata Maresca ◽  
Matteo Radice ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Pseudomonas Syringae ◽  
Rosmarinic Acid ◽  
Plant Protection ◽  
Biological Activities ◽  
Radical Scavenger ◽  
Radical Scavenger Activity ◽  
Antioxidant Agents ◽  
Scavenger Activity

The essential oil (EO), the methanolic (MeOH), and the 70% ethanolic (70% EtOH) extracts obtained from the aerial parts of Ocimum campechianum Mill. (Ecuador) were chemically characterized through gas-chromatography coupled to mass spectrometry detector (GC-MS), high-performance liquid chromatography coupled to diode array-mass spectrometry detectors (HPLC-DAD-MS) and studied for their in vitro biological activity. The radical scavenger activity, performed by spectrophotometric 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, highlighted significant IC50 values for the EO, extracts and their main constituents (eugenol and rosmarinic acid). EO (and eugenol) showed noteworthy activity against Pseudomonas syringae pv. syringae and a moderate effect against clinical Candida strains, with possible synergism in association to fluconazole against the latter microorganisms. The extracts and pure molecules exhibited weak cytotoxic activity against the HaCat cell line and no mutagenicity against Salmonella typhimurium TA98 and TA100 strains, giving indication of safety. Instead, EO showed a weak activity against adenocarcinomic human alveolar basal epithelial cells (A549). The above-mentioned evidence leads us to suggest a potential use of the crude drug, extracts, and EO in cosmetic formulation and food supplements as antioxidant agents. In addition, EO may also have a possible application in plant protection and anti-Candida formulations.

scholarly journals CryoEM at IUCrJ: a new era

IUCrJ ◽  
2016 ◽  
Vol 3 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Sriram Subramaniam ◽  
Werner Kühlbrandt ◽  
Richard Henderson
Keyword(s):  
Electron Cryomicroscopy ◽  
International Union ◽  
New Era ◽  
Future Developments ◽  
Recent Advances ◽  
Natural Home

In this overview, we briefly outline recent advances in electron cryomicroscopy (cryoEM) and explain why the journal IUCrJ, published by the International Union of Crystallography, could provide a natural home for publications covering many present and future developments in the cryoEM field.

scholarly journals Recent Advances in Discovery of Lead Structures from Microbial Natural Products: Genomics- and Metabolomics-Guided Acceleration

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2542
Author(s):  
Linda Sukmarini
Keyword(s):  
Natural Products ◽  
Genome Mining ◽  
Screening Methods ◽  
Technological Advancement ◽  
Natural Origin ◽  
Drug Discovery And Development ◽  
New Methodologies ◽  
Analytical Instrumentation ◽  
Microbial Natural Products ◽  
Drug Leads

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.

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