scholarly journals Novel Alkaloids from Marine Actinobacteria: Discovery and Characterization

Marine Drugs ◽  
2021 ◽  
Vol 20 (1) ◽  
pp. 6
Author(s):  
Anne-Sofie De Rop ◽  
Jeltien Rombaut ◽  
Thomas Willems ◽  
Marilyn De Graeve ◽  
Lynn Vanhaecke ◽  
...  
Keyword(s):  
Natural Products ◽  
Therapeutic Potential ◽  
Genome Mining ◽  
Marine Actinobacteria ◽  
The Past ◽  
Microbial Extracts ◽  
Bioactive Secondary Metabolites ◽  
Experimental Approaches ◽  
Excellent Resource ◽  
Made In

The marine environment is an excellent resource for natural products with therapeutic potential. Its microbial inhabitants, often associated with other marine organisms, are specialized in the synthesis of bioactive secondary metabolites. Similar to their terrestrial counterparts, marine Actinobacteria are a prevalent source of these natural products. Here, we discuss 77 newly discovered alkaloids produced by such marine Actinobacteria between 2017 and mid-2021, as well as the strategies employed in their elucidation. While 12 different classes of alkaloids were unraveled, indoles, diketopiperazines, glutarimides, indolizidines, and pyrroles were most dominant. Discoveries were mainly based on experimental approaches where microbial extracts were analyzed in relation to novel compounds. Although such experimental procedures have proven useful in the past, the methodologies need adaptations to limit the chance of compound rediscovery. On the other hand, genome mining provides a different angle for natural product discovery. While the technology is still relatively young compared to experimental screening, significant improvement has been made in recent years. Together with synthetic biology tools, both genome mining and extract screening provide excellent opportunities for continued drug discovery from marine Actinobacteria.

scholarly journals Recent advances in the genome mining of Aspergillus secondary metabolites (covering 2012–2018)

MedChemComm ◽  
2019 ◽  
Vol 10 (6) ◽  
pp. 840-866 ◽  
Author(s):  
Jillian Romsdahl ◽  
Clay C. C. Wang
Keyword(s):  
Aspergillus Terreus ◽  
Genome Mining ◽  
Gene Clusters ◽  
Genetic Identification ◽  
Biosynthetic Pathways ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
The Past ◽  
Made In

This review covers advances made in genome mining SMs produced by Aspergillus nidulans, Aspergillus fumigatus, Aspergillus niger, and Aspergillus terreus in the past six years (2012–2018). Genetic identification and molecular characterization of SM biosynthetic gene clusters, along with proposed biosynthetic pathways, is discussed in depth.

scholarly journals Back to the Cradle of Cytotherapy: Integrating a Century of Clinical Research and Biotechnology-Based Manufacturing for Modern Tissue-Specific Cellular Treatments in Switzerland

2021 ◽  
Vol 8 (12) ◽  
pp. 221
Author(s):  
Alexis Laurent ◽  
Philippe Abdel-Sayed ◽  
Corinne Scaletta ◽  
Philippe Laurent ◽  
Elénie Laurent ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Past Century ◽  
Clinical Implementation ◽  
The Past ◽  
Health Authorities ◽  
Regulatory Frameworks ◽  
Swiss Health ◽  
Patient Health ◽  
Methodological Aspects ◽  
Made In

Empirically studied by Dr. Brown-Séquard in the late 1800s, cytotherapies were later democratized by Dr. Niehans during the twentieth century in Western Switzerland. Many local cultural landmarks around the Léman Riviera are reminiscent of the inception of such cell-based treatments. Despite the discreet extravagance of the remaining heirs of “living cell therapy” and specific enforcements by Swiss health authorities, current interest in modern and scientifically sound cell-based regenerative medicine has never been stronger. Respective progress made in bioengineering and in biotechnology have enabled the clinical implementation of modern cell-based therapeutic treatments within updated medical and regulatory frameworks. Notably, the Swiss progenitor cell transplantation program has enabled the gathering of two decades of clinical experience in Lausanne for the therapeutic management of cutaneous and musculoskeletal affections, using homologous allogeneic cell-based approaches. While striking conceptual similarities exist between the respective works of the fathers of cytotherapy and of modern highly specialized clinicians, major and important iterative updates have been implemented, centered on product quality and risk-analysis-based patient safety insurance. This perspective article highlights some historical similarities and major evolutive differences, particularly regarding product safety and quality issues, characterizing the use of cell-based therapies in Switzerland over the past century. We outline the vast therapeutic potential to be harnessed for the benefit of overall patient health and the importance of specific scientific methodological aspects.

scholarly journals Genome-Based Studies of Marine Microorganisms to Maximize the Diversity of Natural Products Discovery for Medical Treatments

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Xin-Qing Zhao
Keyword(s):  
Natural Products ◽  
Genome Mining ◽  
Chemical Diversity ◽  
Genomic Research ◽  
Marine Microorganisms ◽  
Genomic Information ◽  
Medical Treatments ◽  
The Past ◽  
Drug Molecules ◽  
Natural Products Discovery

Marine microorganisms are rich source for natural products which play important roles in pharmaceutical industry. Over the past decade, genome-based studies of marine microorganisms have unveiled the tremendous diversity of the producers of natural products and also contributed to the efficiency of harness the strain diversity and chemical diversity, as well as the genetic diversity of marine microorganisms for the rapid discovery and generation of new natural products. In the meantime, genomic information retrieved from marine symbiotic microorganisms can also be employed for the discovery of new medical molecules from yet-unculturable microorganisms. In this paper, the recent progress in the genomic research of marine microorganisms is reviewed; new tools of genome mining as well as the advance in the activation of orphan pathways and metagenomic studies are summarized. Genome-based research of marine microorganisms will maximize the biodiscovery process and solve the problems of supply and sustainability of drug molecules for medical treatments.

A Review of Contamination Issues Associated with an Orbiting Space Station External Environment

1985 ◽  
Vol 28 (1) ◽  
pp. 52-55
Author(s):  
Alphonso Smith
Keyword(s):  
Space Station ◽  
Spacecraft Design ◽  
Contamination Control ◽  
The Past ◽  
Critical Technology ◽  
Experimental Approaches ◽  
Proper Perspective ◽  
Orbiting Spacecraft ◽  
Made In

Contamination monitoring must be placed in the forefront for long-term space exploration experiments in order to help obtain interpretable data. Present day computer program codes have been developed to the stage where they are very useful for contamination modeling and have been used to some extent with the Shuttle Orbiter associated experimental programs. With the upcoming Space Station program, contamination issues must be openly discussed and put into the proper perspective in order to help alleviate some of the associated problems encountered during the Shuttle flight experiments. Issues are discussed relative to ongoing contamination concerns, pointing out some errors of the past and suggesting improvements in experimental approaches to enhance the interpretability of data. The purpose of this article is to focus attention on a critical technology that has been ignored to some extent in past flight experiments. Also, references and data are presented to show that significant efforts have been made in the contamination area. The present need is to make use of the available data and ensure that contamination control guidelines are adhered to. This must be done early in any proposed orbiting spacecraft design and not be added in during critical experimental stages.

scholarly journals Can we intervene in human ageing?

2009 ◽  
Vol 11 ◽  
Author(s):  
Richard G.A. Faragher ◽  
Angela N. Sheerin ◽  
Elizabeth L. Ostler
Keyword(s):  
Progressive Failure ◽  
Ageing Process ◽  
Healthy Life ◽  
The Past ◽  
Human Ageing ◽  
Associated Conditions ◽  
Experimental Approaches ◽  
Eventual Death ◽  
New Hypothesis ◽  
Made In

Ageing is a progressive failure of defence and repair processes that produces physiological frailty (the loss of organ reserve with age), loss of homeostasis and eventual death. Over the past ten years exceptional progress has been made in understanding both why the ageing process happens and the mechanisms that are responsible for it. The study of natural mutants that accelerate some, but not all, of the features of the human ageing process has now progressed to a degree that drug trials are either taking place or can be envisaged. Simultaneously, a series of mutations have been identified in different species that confer extended healthy life, indicating that the ageing process is much more malleable than might have been expected and that single interventions have the potential to delay the onset of multiple age-associated conditions. Data generated using these organisms have led to the formulation of a powerful new hypothesis, the ‘green theory’ of ageing. This proposes that a finite capacity to carry out broad-spectrum detoxification and recycling is the primary mechanistic limit on organismal lifespan. This is turn suggests important new experimental approaches and potential interventions designed to increase healthy lifespan.

scholarly journals Resistance-guided mining of bacterial genotoxins defines a family of DNA glycosylases

2021 ◽  
Author(s):  
Noah P Bradley ◽  
Katherine L Wahl ◽  
Jacob L Steenwyk ◽  
Antonis Rokas ◽  
Brandt F. Eichman
Keyword(s):  
Natural Products ◽  
Dna Adducts ◽  
Therapeutic Potential ◽  
Genome Mining ◽  
Gene Clusters ◽  
Dna Glycosylases ◽  
Biosynthetic Gene Clusters ◽  
Repair Enzymes ◽  
Genotoxic Compounds ◽  
Azinomycin B

Unique DNA repair enzymes that provide self-resistance against genotoxic natural products have been discovered recently in bacterial biosynthetic gene clusters (BGCs). The DNA glycosylase AlkZ belongs to a superfamily of uncharacterized proteins found in antibiotic producers and pathogens, but despite its importance to azinomycin B resistance, the roles of AlkZ orthologs in production of other natural products are unknown. Here, we analyze the genomic distribution and use a resistance-based genome mining approach to identify Streptomyces AlkZ homologs associated with known and uncharacterized BGCs. We show that the ortholog associated with synthesis of the alkylating agent hedamycin excises hedamycin-DNA adducts and provides resistance to the genotoxin in cells. Our results define AlkZ in self-resistance to specific antimicrobials and implicate a related but distinct homolog, which we name AlkX, in protection against an array of genotoxins. This work provides a framework for targeted discovery of new genotoxic compounds with therapeutic potential.

Expanding the Natural Products Heterologous Expression Repertoire in the Model Cyanobacterium Anabaena sp. Strain PCC 7120: Production of Pendolmycin and Teleocidin B-4

2019 ◽  
Author(s):  
Patrick Videau ◽  
Kaitlyn Wells ◽  
Arun Singh ◽  
Jessie Eiting ◽  
Philip Proteau ◽  
...  
Keyword(s):  
Natural Products ◽  
Genome Mining ◽  
Gene Clusters ◽  
Combinatorial Biosynthesis ◽  
Test Case ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Cyanobacterium Anabaena ◽  
Anabaena Sp ◽  
Pcc 7120

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.

South Asian Developmental Crisis (Review Article)

1973 ◽  
Vol 12 (2) ◽  
pp. 181-188
Author(s):  
Rafiq Ahmad
Keyword(s):  
Second World War ◽  
World War ◽  
The Past ◽  
The Great Depression ◽  
Political Independence ◽  
Integrated Theory ◽  
Pass Through ◽  
Developed World ◽  
Second World ◽  
Made In

Like nations and civilizations, sciences also pass through period of crises when established theories are overthrown by the unpredictable behaviour of events. Economics is passing through such a crisis. The challenge thrown by the Great Depression of early 1930s took a decade before Keynes re-established the supremacy of economics. But this supremacy has again been upset by the crisis of poverty in the vast under-developed world which attained political independence after the Second World War. Poverty had always existed but never before had it been of such concern to economists as during the past twenty five years or so. Economic literature dealing with this problem has piled up but so have the agonies of poverty. No plausible and well-integrated theory of economic development or under-development has emerged so far, though brilliant advances have been made in isolated directions.

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