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      Adding Zooplankton to the OSMAC Toolkit: Effect of Grazing Stress on the Metabolic Profile and Bioactivity of a Diatom

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          Abstract

          “One strain many compounds” (OSMAC) based approaches have been widely used in the search for bioactive compounds. Introducing stress factors like nutrient limitation, UV-light or cocultivation with competing organisms has successfully been used in prokaryote cultivation. It is known that diatom physiology is affected by changed cultivation conditions such as temperature, nutrient concentration and light conditions. Cocultivation, though, is less explored. Hence, we wanted to investigate whether grazing pressure can affect the metabolome of the marine diatom Porosira glacialis, and if the stress reaction could be detected as changes in bioactivity. P. glacialis cultures were mass cultivated in large volume bioreactor (6000 L), first as a monoculture and then as a coculture with live zooplankton. Extracts of the diatom biomass were screened in a selection of bioactivity assays: inhibition of biofilm formation, antibacterial and cell viability assay on human cells. Bioactivity was found in all bioassays performed. The viability assay towards normal lung fibroblasts revealed that P. glacialis had higher bioactivity when cocultivated with zooplankton than in monoculture. Cocultivation with diatoms had no noticeable effect on the activity against biofilm formation or bacterial growth. The metabolic profiles were analyzed showing the differences in diatom metabolomes between the two culture conditions. The experiment demonstrates that grazing stress affects the biochemistry of P. glacialis and thus represents a potential tool in the OSMAC toolkit.

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          SCARED TO DEATH? THE EFFECTS OF INTIMIDATION AND CONSUMPTION IN PREDATOR–PREY INTERACTIONS

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            Big effects from small changes: possible ways to explore nature's chemical diversity.

            Fungi or bacteria that produce secondary metabolites often have the potential to bring up various compounds from a single strain. The molecular basis for this well-known observation was confirmed in the last few years by several sequencing projects of different microorganisms. Besides well-known examples about induction of a selected biosynthesis (for example, by high- or low-phosphate cultivation media), no overview about the potential in this field for finding natural products was given. We have investigated the systematic alteration of easily accessible cultivation parameters (for example, media composition, aeration, culture vessel, addition of enzyme inhibitors) in order to increase the number of secondary metabolites available from one microbial source. We termed this way of revealing nature's chemical diversity the 'OSMAC (One Strain-Many Compounds) approach' and by using it we were able to isolate up to 20 different metabolites in yields up to 2.6 g L(-1) from a single organism. These compounds cover nearly all major natural product families, and in some cases the high production titer opens new possibilities for semisynthetic methods to enhance even more the chemical diversity of selected compounds. The OSMAC approach offers a good alternative to industrial high-throughput screening that focuses on the active principle in a distinct bioassay. In consequence, the detection of additional compounds that might be of interest as lead structures in further bioassays is impossible and clearly demonstrates the deficiency of the industrial procedure. Furthermore, our approach seems to be a useful tool to detect those metabolites that are postulated to be the final products of an amazing number of typical secondary metabolite gene clusters identified in several microorganisms. If one assumes a (more or less) defined reservoir of genetic possibilities for several biosynthetic pathways in one strain that is used for a highly flexible production of secondary metabolites depending on the environment, the OSMAC approach might give more insight into the role of secondary metabolism in the microbial community or during the evolution of life itself.
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              Emerging applications of metabolomics in drug discovery and precision medicine.

              Metabolomics is an emerging 'omics' science involving the comprehensive characterization of metabolites and metabolism in biological systems. Recent advances in metabolomics technologies are leading to a growing number of mainstream biomedical applications. In particular, metabolomics is increasingly being used to diagnose disease, understand disease mechanisms, identify novel drug targets, customize drug treatments and monitor therapeutic outcomes. This Review discusses some of the latest technological advances in metabolomics, focusing on the application of metabolomics towards uncovering the underlying causes of complex diseases (such as atherosclerosis, cancer and diabetes), the growing role of metabolomics in drug discovery and its potential effect on precision medicine.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Mar Drugs
                Mar Drugs
                marinedrugs
                Marine Drugs
                MDPI
                1660-3397
                03 February 2021
                February 2021
                : 19
                : 2
                : 87
                Affiliations
                [1 ]Marbio, Norwegian College of Fishery Science, Faculty of Biosciences, Fisheries and Economics, UiT–The Arctic University of Norway, N-9037 Tromsø, Norway; jeanette.h.andersen@ 123456uit.no (J.H.A.); espen.hansen@ 123456uit.no (E.H.H.)
                [2 ]Microalgae and Microbiomes, Norwegian College of Fishery Science, Faculty of Biosciences, Fisheries and Economics, UiT–The Arctic University of Norway, N-9037 Tromsø, Norway; richard.a.ingebrigtsen@ 123456uit.no (R.A.I.); hei000@ 123456post.uit.no (H.C.E.)
                [3 ]Arctic Marine System Ecology, Department of Arctic and Marine Biology, Faculty of Biosciences, Fisheries and Economics, UiT–The Arctic University of Norway, N-9037 Tromsø, Norway; fredrika.norrbin@ 123456uit.no
                Author notes
                [* ]Correspondence: renate.d.osvik@ 123456uit.no ; Tel.: +47-776-49-265
                Author information
                https://orcid.org/0000-0001-8893-9394
                https://orcid.org/0000-0002-2871-8888
                https://orcid.org/0000-0001-5062-5138
                https://orcid.org/0000-0002-6059-060X
                https://orcid.org/0000-0003-0354-986X
                Article
                marinedrugs-19-00087
                10.3390/md19020087
                7913365
                33546196
                2b948113-7474-4709-b5c2-a617388a44e7
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 December 2020
                : 29 January 2021
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                diatoms,microalgae,biotechnology,biodiscovery,osmac,cultivation
                Pharmacology & Pharmaceutical medicine
                diatoms, microalgae, biotechnology, biodiscovery, osmac, cultivation

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