scholarly journals High Value Phycotoxins From the Dinoflagellate Prorocentrum

2021 ◽  
Vol 8 ◽  
Author(s):  
Dolores Camacho-Muñoz ◽  
Radisti A. Praptiwi ◽  
Linda A. Lawton ◽  
Christine Edwards

Marine dinoflagellates produce chemically diverse compounds, with a wide range of biological activity (antimicrobial, anticancer, treatment of neurodegenerative disease along with use as biomedical research tools). Chemical diversity is highlighted by their production of molecules such as the saxitoxin family of alkaloids (C10H17N7O4 – 299 g/mol) to the amphipathic maitotoxin (C164H256O68S2Na2 – 3,422 g/mol), representing one of the largest and most complex secondary metabolites characterized. Dinoflagellates, are most well-known for the production of red tides which are frequently toxic, including okadaic acid and related dinophysistoxins, which are tumor promoters. The mode of action for these phycotoxins, is by specific inhibition of protein phosphatases, enzymes essential in regulation of many cellular processes. Hence, these compounds are being used for vital cell regulation studies. However, the availability of useful amounts of these compounds has restricted research. Chemical synthesis of some compounds such as okadaic acid has been investigated, but the complexity of the molecule resulted in many lengthy steps and achieved only a poor yield. The use of naturally occurring phytoplankton has been investigated as a potential source of these compounds, but it has been shown to be unreliable and impractical. The most practical option is large scale culture with down-stream processing/purification which requires specialist facilities and expertise. This review, describes the biotechnological potential of these organisms and the challenges to achieve useful yields of high quality phycotoxins using Prorocentrum spp. as an example to produce okadaic acid.

2019 ◽  
Author(s):  
Vít Nováček ◽  
Gavin McGauran ◽  
David Matallanas ◽  
Adrián Vallejo Blanco ◽  
Piero Conca ◽  
...  

AbstractPhosphorylation of specific substrates by protein kinases is a key control mechanism for vital cell-fate decisions and other cellular processes. However, discovering specific kinase-substrate relationships is timeconsuming and often rather serendipitous. Computational predictions alleviate these challenges, but the current approaches suffer from limitations like restricted kinome coverage and inaccuracy. They also typically utilise only local features without reflecting broader interaction context. To address these limitations, we have developed an alternative predictive model. It uses statistical relational learning on top of phosphorylation networks interpreted as knowledge graphs, a simple yet robust model for representing networked knowledge. Compared to a representative selection of six existing systems, our model has the highest kinome coverage and produces biologically valid high-confidence predictions not possible with the other tools. Specifically, we have experimentally validated predictions of previously unknown phosphorylations by the LATS1, AKT1, PKA and MST2 kinases in human. Thus, our tool is useful for focusing phosphoproteomic experiments, and facilitates the discovery of new phosphorylation reactions. Our model can be accessed publicly via an easy-to-use web interface (LinkPhinder).Author SummaryLinkPhinder is a new approach to prediction of protein signalling networks based on kinase-substrate relationships that outperforms existing approaches. Phosphorylation networks govern virtually all fundamental biochemical processes in cells, and thus have moved into the centre of interest in biology, medicine and drug development. Fundamentally different from current approaches, LinkPhinder is inherently network-based and makes use of the most recent AI de-velopments. We represent existing phosphorylation data as knowledge graphs, a format for large-scale and robust knowledge representation. Training a link prediction model on such a structure leads to novel, biologically valid phosphorylation network predictions that cannot be made with competing tools. Thus our new conceptual approach can lead to establishing a new niche of AI applications in computational biology.


2015 ◽  
Vol 112 (45) ◽  
pp. 13952-13957 ◽  
Author(s):  
Maureen E. Hillenmeyer ◽  
Gergana A. Vandova ◽  
Erin E. Berlew ◽  
Louise K. Charkoudian

Natural product biosynthetic pathways generate molecules of enormous structural complexity and exquisitely tuned biological activities. Studies of natural products have led to the discovery of many pharmaceutical agents, particularly antibiotics. Attempts to harness the catalytic prowess of biosynthetic enzyme systems, for both compound discovery and engineering, have been limited by a poor understanding of the evolution of the underlying gene clusters. We developed an approach to study the evolution of biosynthetic genes on a cluster-wide scale, integrating pairwise gene coevolution information with large-scale phylogenetic analysis. We used this method to infer the evolution of type II polyketide gene clusters, tracing the path of evolution from the single ancestor to those gene clusters surviving today. We identified 10 key gene types in these clusters, most of which were swapped in from existing cellular processes and subsequently specialized. The ancestral type II polyketide gene cluster likely comprised a core set of five genes, a roster that expanded and contracted throughout evolution. A key C24 ancestor diversified into major classes of longer and shorter chain length systems, from which a C20 ancestor gave rise to the majority of characterized type II polyketide antibiotics. Our findings reveal that (i) type II polyketide structure is predictable from its gene roster, (ii) only certain gene combinations are compatible, and (iii) gene swaps were likely a key to evolution of chemical diversity. The lessons learned about how natural selection drives polyketide chemical innovation can be applied to the rational design and guided discovery of chemicals with desired structures and properties.


2020 ◽  
Vol 24 (24) ◽  
pp. 2865-2901
Author(s):  
Hidayat Hussain ◽  
Iftikhar Ali ◽  
Elizbit ◽  
Wahid Hussain ◽  
Nilufar Z. Mamadalieva ◽  
...  

: Fungi have provided intriguing chemical diversity and have additionally proven to be a tremendous source for a great variety of therapeutic molecules. Various fungal glycosides have been reported from fungi and the majority of these metabolites possess cytotoxic and antimicrobial effects. Although natural products are obtained in most cases in small amounts from the specific natural source, total syntheses of these valuable commodities remain one of the most important ways of obtaining them on a large scale for more detailed and comprehensive biological studies. In addition, the total synthesis of secondary metabolites is a useful tool, not only for the disclosure of novel complex pharmacologically active molecules but also for the establishment of cutting-edge methodologies in synthetic chemistry. Numerous fungal glycosides have been synthesized in the last four decades regarding the following natural product classes viz., tetramic acid glycosides (epicoccamides A and D), polyketide glycosides (TMC-151C), 2-pyrone glycosides (epipyrone A), diterpene glycosides (sordarin), depside glycosides (CRM646-A and –B, KS-501 and KS- 502), caloporosides (caloporoside A), glycolipids (emmyguyacins A and B, acremomannolipin A), and cerebrosides (cerebroside B, Asperamide B, phalluside-1, Sch II). The current literature review about fungal glycoside synthetic studies is, therefore, of interest for a wide range of scientists and researchers in the field of organic, natural product, and medicinal chemists as it outlines key strategies of fungal glycosides and, in particular, glycosylation, the known biological and pharmacological effects of these natural compounds have afforded a new dimension of exposure.


2020 ◽  
Author(s):  
Victòria Pascal Andreu ◽  
Michael A. Fischbach ◽  
Marnix H. Medema

ABSTRACTThe gut contains an enormous diversity of simple as well as complex molecules from highly diverse food sources as well as host-secreted molecules. This presents a large metabolic opportunity for the gut microbiota, but little is known on how gut microbes are able to catabolize this large chemical diversity. Recently, Fe-S flavoenzymes were found to be key in the transformation of bile acids, catalysing the key step in the 7α-dehydroxylation pathway that allows gut bacteria to transform cholic acid (CA) into deoxycholic acid (DCA), an exclusively microbe-derived molecule with major implications for human health. While this enzyme family has also been implicated in a limited number of other catalytic transformations, little is known about the extent to which it is of more global importance in gut microbial metabolism. Here, we use large-scale computational genomic analysis to show that this enzyme superfamily has undergone a remarkable expansion in Clostridiales, and occurs throughout a diverse array of >1,000 different families of putative metabolic gene clusters. Analysis of the enzyme content of these gene clusters suggests that they encode pathways with a wide range of predicted substrate classes, including saccharides, amino acids/peptides and lipids. Altogether, these results indicate a potentially important role of this protein superfamily in the human gut, and our dataset provides significant opportunities for the discovery of novel pathways that may have significant effects on human health.


Author(s):  
V. C. Kannan ◽  
A. K. Singh ◽  
R. B. Irwin ◽  
S. Chittipeddi ◽  
F. D. Nkansah ◽  
...  

Titanium nitride (TiN) films have historically been used as diffusion barrier between silicon and aluminum, as an adhesion layer for tungsten deposition and as an interconnect material etc. Recently, the role of TiN films as contact barriers in very large scale silicon integrated circuits (VLSI) has been extensively studied. TiN films have resistivities on the order of 20μ Ω-cm which is much lower than that of titanium (nearly 66μ Ω-cm). Deposited TiN films show resistivities which vary from 20 to 100μ Ω-cm depending upon the type of deposition and process conditions. TiNx is known to have a NaCl type crystal structure for a wide range of compositions. Change in color from metallic luster to gold reflects the stabilization of the TiNx (FCC) phase over the close packed Ti(N) hexagonal phase. It was found that TiN (1:1) ideal composition with the FCC (NaCl-type) structure gives the best electrical property.


Author(s):  
О. Кravchuk ◽  
V. Symonenkov ◽  
I. Symonenkova ◽  
O. Hryhorev

Today, more than forty countries of the world are engaged in the development of military-purpose robots. A number of unique mobile robots with a wide range of capabilities are already being used by combat and intelligence units of the Armed forces of the developed world countries to conduct battlefield intelligence and support tactical groups. At present, the issue of using the latest information technology in the field of military robotics is thoroughly investigated, and the creation of highly effective information management systems in the land-mobile robotic complexes has acquired a new phase associated with the use of distributed information and sensory systems and consists in the transition from application of separate sensors and devices to the construction of modular information subsystems, which provide the availability of various data sources and complex methods of information processing. The purpose of the article is to investigate the ways to increase the autonomy of the land-mobile robotic complexes using in a non-deterministic conditions of modern combat. Relevance of researches is connected with the necessity of creation of highly effective information and control systems in the perspective robotic means for the needs of Land Forces of Ukraine. The development of the Armed Forces of Ukraine management system based on the criteria adopted by the EU and NATO member states is one of the main directions of increasing the effectiveness of the use of forces (forces), which involves achieving the principles and standards necessary for Ukraine to become a member of the EU and NATO. The inherent features of achieving these criteria will be the transition to a reduction of tasks of the combined-arms units and the large-scale use of high-precision weapons and land remote-controlled robotic devices. According to the views of the leading specialists in the field of robotics, the automation of information subsystems and components of the land-mobile robotic complexes can increase safety, reliability, error-tolerance and the effectiveness of the use of robotic means by standardizing the necessary actions with minimal human intervention, that is, a significant increase in the autonomy of the land-mobile robotic complexes for the needs of Land Forces of Ukraine.


1994 ◽  
Vol 29 (12) ◽  
pp. 149-156 ◽  
Author(s):  
Marcus Höfken ◽  
Katharina Zähringer ◽  
Franz Bischof

A novel agitating system has been developed which allows for individual or combined operation of stirring and aeration processes. Basic fluid mechanical considerations led to the innovative hyperboloid design of the stirrer body, which ensures high efficiencies in the stirring and the aeration mode, gentle circulation with low shear forces, excellent controllability, and a wide range of applications. This paper presents the basic considerations which led to the operating principle, the technical realization of the system and experimental results in a large-scale plant. The characteristics of the system and the differences to other stirring and aeration systems are illustrated. Details of the technical realization are shown, which conform to the specific demands of applications in the biological treatment of waste water. Special regard is given to applications in the upgrading of small compact waste water treatment plants.


2012 ◽  
Vol 9 (1) ◽  
pp. 175-180
Author(s):  
Yu.D. Chashechkin

According to the results of visualization of streams, the existence of structures in a wide range of scales is noted: from galactic to micron. The use of a fundamental system of equations is substantiated based on the results of comparing symmetries of various flow models with the usage of theoretical group methods. Complete solutions of the system are found by the methods of the singular perturbations theory with a condition of compatibility, which determines the characteristic equation. A comparison of complete solutions with experimental data shows that regular solutions characterize large-scale components of the flow, a rich family of singular solutions describes formation of the thin media structure. Examples of calculations and observations of stratified, rotating and multiphase media are given. The requirements for the technique of an adequate experiment are discussed.


2019 ◽  
Vol 26 (10) ◽  
pp. 720-742 ◽  
Author(s):  
Kaushik Das ◽  
Karabi Datta ◽  
Subhasis Karmakar ◽  
Swapan K. Datta

Antimicrobial Peptides (AMPs) have diverse structures, varied modes of actions, and can inhibit the growth of a wide range of pathogens at low concentrations. Plants are constantly under attack by a wide range of phytopathogens causing massive yield losses worldwide. To combat these pathogens, nature has armed plants with a battery of defense responses including Antimicrobial Peptides (AMPs). These peptides form a vital component of the two-tier plant defense system. They are constitutively expressed as part of the pre-existing first line of defense against pathogen entry. When a pathogen overcomes this barrier, it faces the inducible defense system, which responds to specific molecular or effector patterns by launching an arsenal of defense responses including the production of AMPs. This review emphasizes the structural and functional aspects of different plant-derived AMPs, their homology with AMPs from other organisms, and how their biotechnological potential could generate durable resistance in a wide range of crops against different classes of phytopathogens in an environmentally friendly way without phenotypic cost.


Author(s):  
Eun-Young Mun ◽  
Anne E. Ray

Integrative data analysis (IDA) is a promising new approach in psychological research and has been well received in the field of alcohol research. This chapter provides a larger unifying research synthesis framework for IDA. Major advantages of IDA of individual participant-level data include better and more flexible ways to examine subgroups, model complex relationships, deal with methodological and clinical heterogeneity, and examine infrequently occurring behaviors. However, between-study heterogeneity in measures, designs, and samples and systematic study-level missing data are significant barriers to IDA and, more broadly, to large-scale research synthesis. Based on the authors’ experience working on the Project INTEGRATE data set, which combined individual participant-level data from 24 independent college brief alcohol intervention studies, it is also recognized that IDA investigations require a wide range of expertise and considerable resources and that some minimum standards for reporting IDA studies may be needed to improve transparency and quality of evidence.


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