Database for Rapid Dereplication of Known Natural Products Using Data from MS and Fast NMR Experiments

Zani, Carlos L.; Carroll, Anthony R.

doi:10.1021/acs.jnatprod.6b01093

Cited by 48 publications

(44 citation statements)

References 37 publications

(44 reference statements)

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“…In fact, the last decade has seen the development of several databases providing systematic collection of information that focuses on natural compounds themselves, offering the possibility of searching structure, source, and mechanisms of action of the searched compounds. For example, DEREP-NP is a database that compiles structural data (Zani and Carroll, 2017). An interesting review from Xie et al (2015) allows the comparison of fourteen of these databases focusing on NP, balancing their advantages and disadvantages.…”

Section: At the Development Stage: Systematic Inventories Of Natural mentioning

confidence: 99%

Unraveling Plant Natural Chemical Diversity for Drug Discovery Purposes

Lautié

Russo²,

Ducrot³

et al. 2020

Front. Pharmacol.

110

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The screening and testing of extracts against a variety of pharmacological targets in order to benefit from the immense natural chemical diversity is a concern in many laboratories worldwide. And several successes have been recorded in finding new actives in natural products, some of which have become new drugs or new sources of inspiration for drugs. But in view of the vast amount of research on the subject, it is surprising that not more drug candidates were found. In our view, it is fundamental to reflect upon the approaches of such drug discovery programs and the technical processes that are used, along with their inherent difficulties and biases. Based on an extensive survey of recent publications, we discuss the origin and the variety of natural chemical diversity as well as the strategies to having the potential to embrace this diversity. It seemed to us that some of the difficulties of the area could be related with the technical approaches that are used, so the present review begins with synthetizing some of the more used discovery strategies, exemplifying some key points, in order to address some of their limitations. It appears that one of the challenges of natural product-based drug discovery programs should be an easier access to renewable sources of plant-derived products. Maximizing the use of the data together with the exploration of chemical diversity while working on reasonable supply of natural product-based entities could be a way to answer this challenge. We suggested alternative ways to access and explore part of this chemical diversity with in vitro cultures. We also reinforced how important it was organizing and making available this worldwide knowledge in an "inventory" of natural products and their sources. And finally, we focused on strategies based on synthetic biology and syntheses that allow reaching industrial scale supply. Approaches based on the opportunities lying in untapped natural plant chemical diversity are also considered.

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“…For annotated mass spectral information, see Supplementary Data file. The predicted molecular formulas of the chlorine-iodine containing metabolites were searched against several external mass spectral and natural product databases, including DEREP-NP 54 and COCONUT 55 (for a full list see Supplementary Table 7). The occurrence of iodine-containing metabolites in bags 3 and 4 at the end of the E. huxleyi demise phase (day 23) was compared by plotting the extracted ion chromatogram (EIC) of the iodide fragment (m/z 126.90) in negative ionization mode using the high-energy scan function (MassLynx, version 4.1, Waters).…”

Section: Structural Characterization Of the Vdom Metabolitesmentioning

confidence: 99%

Viral infection of algal blooms leaves a halogenated footprint on the dissolved organic matter in the ocean

Kuhlisch

Schleyer

Shahaf

et al. 2020

Preprint

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Algal blooms are important hotspots of primary production in the ocean, forming the basis of the marine food web and fueling the pool of dissolved organic matter (DOM)1, which is the largest global inventory of reduced carbon and a market place for metabolic exchange in the ocean2. Marine viruses are key players in controlling algal bloom demise and act as major biogeochemical drivers of nutrient cycling and metabolic fluxes by shunting algal biomass from higher trophic levels to the DOM pool, a process termed the ‘viral shunt’3,4. Nevertheless, the metabolic composition of virus-induced DOM (vDOM) in the marine environment is unknown. To decode the metabolic footprint of the ‘viral shunt’, we induced a bloom of the ecologically important alga Emiliania huxleyi in the natural environment, and followed its succession using an untargeted exometabolomics approach. Here we show that algal bloom succession induces extensive and dynamic changes in the exometabolic landscape, especially during bloom demise. By correlating to a specific viral gene marker, we discovered a set of novel chlorine-iodine-containing metabolites that were induced by viral infection and copiously released during bloom demise. We further detected several of these chloro-iodo metabolites in virus-infected open ocean blooms of E. huxleyi, supporting their use as sensitive biomarkers for virus-induced demise in the natural environment. Therefore, we propose halogenation to be a hallmark of the E. huxleyi vDOM, providing insights into the profound metabolic consequences of viral infection for the marine DOM pool.

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“…Compound dereplication is one of the big hurdles in the discovery of MNPs. To achieve a simpler, faster, and more effective compound dereplication, the collected data in these databases include computational data from bioinformatics, compound curation and compilation, and experimental data from UV spectroscopy, mass spectroscopy, and nuclear magnetic resonance (NMR) . These databases deliver crucial information to the scientific community to discover new MNPs.…”

Section: Available Databases Of Mnpsmentioning

confidence: 99%

“…To achieve a simpler, faster, and more effective compound dereplication, the collected data in these databases include computational data from bioinformatics, compound curation and compilation, [16][17][18][19]34,35] and experimental data from UV spectroscopy, [34] mass spectroscopy, [20] and nuclear magnetic resonance (NMR). [36] These databases deliver crucial information to the scientific community to discover new MNPs. Yet, access fees may prevent their broader access to academic research and small companies.…”

Section: Paid-access Databases Of Marine Natural Productsmentioning

confidence: 99%

Free Marine Natural Products Databases for Biotechnology and Bioengineering

Barbosa

Roque

2019

Biotechnol. J.

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Marine organisms and micro‐organisms are a source of natural compounds with unique chemical features. These chemical properties are useful for the discovery of new functions and applications of marine natural products (MNPs). To extensively exploit the potential implementations of MNPs, they are gathered in chemical databases that allow their study and screening for applications of biotechnological interest. However, the classification of MNPs is currently poor in generic chemical databases. The present availability of free‐access‐focused MNP databases is scarce and the molecular diversity of these databases is still very low when compared to the paid‐access ones. In this review paper, the current scenario of free‐access MNP databases is presented as well as the hindrances involved in their development, mainly compound dereplication. Examples and opportunities for using freely accessible MNP databases in several important areas of biotechnology are also assessed. The scope of this paper is, as well, to notify the latent potential of these information sources for the discovery and development of new MNPs in biotechnology, and push future efforts to develop a public domain MNP database freely available for the scientific community.

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“…Typical estimates of the number of different molecules in natural products quote values such as 200 000 or more (e.g.,), and natural products remain an important source of leads for successful drug discovery (e.g.,). What fraction of natural products remain undiscovered is of course unknown, but the existing numbers are already sufficiently great that structure reproduction, rediscovery, and “dereplication” are significant issues.…”

Section: Introductionmentioning

confidence: 99%

Analysing and Navigating Natural Products Space for Generating Small, Diverse, But Representative Chemical Libraries

O'Hagan

Kell

2017

Biotechnol. J.

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Armed with the digital availability of two natural products libraries, amounting to some 195 885 molecular entities, we ask the question of how we can best sample from them to maximize their "representativeness" in smaller and more usable libraries of 96, 384, 1152, and 1920 molecules. The term "representativeness" is intended to include diversity, but for numerical reasons (and the likelihood of being able to perform a QSAR) it is necessary to focus on areas of chemical space that are more highly populated. Encoding chemical structures as fingerprints using the RDKit "patterned" algorithm, we first assess the granularity of the natural products space using a simple clustering algorithm, showing that there are major regions of "denseness" but also a great many very sparsely populated areas. We then apply a "hybrid" hierarchical K-means clustering algorithm to the data to produce more statistically robust clusters from which representative and appropriate numbers of samples may be chosen. There is necessarily again a trade-off between cluster size and cluster number, but within these constraints, libraries containing 384 or 1152 molecules can be found that come from clusters that represent some 18 and 30% of the whole chemical space, with cluster sizes of, respectively, 50 and 27 or above, just about sufficient to perform a QSAR. By using the online availability of molecules via the Molport system (www.molport.com), we are also able to construct (and, for the first time, provide the contents of ) a small virtual library of available molecules that provided effective coverage of the chemical space described. Consistent with this, the average molecular similarities of the contents of the libraries developed is considerably smaller than is that of the original libraries. The suggested libraries may have use in molecular or phenotypic screening, including for determining possible transporter substrates.

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Database for Rapid Dereplication of Known Natural Products Using Data from MS and Fast NMR Experiments

Cited by 48 publications

References 37 publications

Unraveling Plant Natural Chemical Diversity for Drug Discovery Purposes

Viral infection of algal blooms leaves a halogenated footprint on the dissolved organic matter in the ocean

Free Marine Natural Products Databases for Biotechnology and Bioengineering

Analysing and Navigating Natural Products Space for Generating Small, Diverse, But Representative Chemical Libraries

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