67
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Extending the “One Strain Many Compounds” (OSMAC) Principle to Marine Microorganisms

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Genomic data often highlights an inconsistency between the number of gene clusters identified using bioinformatic approaches as potentially producing secondary metabolites and the actual number of chemically characterized secondary metabolites produced by any given microorganism. Such gene clusters are generally considered as “silent”, meaning that they are not expressed under laboratory conditions. Triggering expression of these “silent” clusters could result in unlocking the chemical diversity they control, allowing the discovery of novel molecules of both medical and biotechnological interest. Therefore, both genetic and cultivation-based techniques have been developed aimed at stimulating expression of these “silent” genes. The principles behind the cultivation based approaches have been conceptualized in the “one strain many compounds” (OSMAC) framework, which underlines how a single strain can produce different molecules when grown under different environmental conditions. Parameters such as, nutrient content, temperature, and rate of aeration can be easily changed, altering the global physiology of a microbial strain and in turn significantly affecting its secondary metabolism. As a direct extension of such approaches, co-cultivation strategies and the addition of chemical elicitors have also been used as cues to activate “silent” clusters. In this review, we aim to provide a focused and comprehensive overview of these strategies as they pertain to marine microbes. Moreover, we underline how changes in some parameters which have provided important results in terrestrial microbes, but which have rarely been considered in marine microorganisms, may represent additional strategies to awaken “silent” gene clusters in marine microbes. Unfortunately, the empirical nature of the OSMAC approach forces scientists to perform extensive laboratory experiments. Nevertheless, we believe that some computation and experimental based techniques which are used in other disciplines, and which we discuss; could be effectively employed to help streamline the OSMAC based approaches. We believe that natural products discovery in marine microorganisms would be greatly aided through the integration of basic microbiological approaches, computational methods, and technological innovations, thereby helping unearth much of the as yet untapped potential of these microorganisms.

          Related collections

          Most cited references134

          • Record: found
          • Abstract: found
          • Article: not found

          Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).

          Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters.

            Although biosynthetic gene clusters (BGCs) have been discovered for hundreds of bacterial metabolites, our knowledge of their diversity remains limited. Here, we used a novel algorithm to systematically identify BGCs in the extensive extant microbial sequencing data. Network analysis of the predicted BGCs revealed large gene cluster families, the vast majority uncharacterized. We experimentally characterized the most prominent family, consisting of two subfamilies of hundreds of BGCs distributed throughout the Proteobacteria; their products are aryl polyenes, lipids with an aryl head group conjugated to a polyene tail. We identified a distant relationship to a third subfamily of aryl polyene BGCs, and together the three subfamilies represent the largest known family of biosynthetic gene clusters, with more than 1,000 members. Although these clusters are widely divergent in sequence, their small molecule products are remarkably conserved, indicating for the first time the important roles these compounds play in Gram-negative cell biology. Copyright © 2014 Elsevier Inc. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Regulation of fungal secondary metabolism.

              Fungi produce a multitude of low-molecular-mass compounds known as secondary metabolites, which have roles in a range of cellular processes such as transcription, development and intercellular communication. In addition, many of these compounds now have important applications, for instance, as antibiotics or immunosuppressants. Genome mining efforts indicate that the capability of fungi to produce secondary metabolites has been substantially underestimated because many of the fungal secondary metabolite biosynthesis gene clusters are silent under standard cultivation conditions. In this Review, I describe our current understanding of the regulatory elements that modulate the transcription of genes involved in secondary metabolism. I also discuss how an improved knowledge of these regulatory elements will ultimately lead to a better understanding of the physiological and ecological functions of these important compounds and will pave the way for a novel avenue to drug discovery through targeted activation of silent gene clusters.
                Bookmark

                Author and article information

                Journal
                Mar Drugs
                Mar Drugs
                marinedrugs
                Marine Drugs
                MDPI
                1660-3397
                23 July 2018
                July 2018
                : 16
                : 7
                : 244
                Affiliations
                [1 ]Division of Microbial Ecology, Department of Microbiology and Ecosystem Science, Althanstraße 14, 1090 Vienna, Austria
                [2 ]School of Microbiology, University College Cork, National University of Ireland, T12 YN60 Cork, Ireland; sjackson@ 123456ucc.ie (S.A.J.); sloane.patry@ 123456gmail.com (S.P.)
                [3 ]Environmental Research Institute, University College Cork, National University of Ireland, Lee Road, T23 XE10 Cork, Ireland
                Author notes
                [* ]Correspondence: stfn.romano@ 123456gmail.com (S.R.); a.dobson@ 123456ucc.ie (A.D.W.D.); Tel.: +353-21-490-2743 (A.D.W.D.)
                Author information
                https://orcid.org/0000-0002-7600-1953
                https://orcid.org/0000-0001-7869-9032
                https://orcid.org/0000-0001-8300-5760
                https://orcid.org/0000-0002-7713-5574
                Article
                marinedrugs-16-00244
                10.3390/md16070244
                6070831
                30041461
                c4705d10-3764-408b-a7b4-7544364e9de9
                © 2018 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
                : 05 July 2018
                : 19 July 2018
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                secondary metabolites,biosynthetic gene clusters,cultivation,environmental cues,co-cultivation,chemical elicitors,one strain many compounds,osmac

                Comments

                Comment on this article