Isolation and Identification of Bioactive Secondary Metabolites from Salinispora Arenicola Obtained from Ocean Sediments from the Madeira Archipelago
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Marine Sediment Recovered Salinispora Sp. Inhibits the Growth of Emerging Bacterial Pathogens and Other Multi-Drug-Resistant Bacteria
Polish Journal of Microbiology ORIGINAL PAPER 2020, Vol. 69, No 3, 321–330 https://doi.org/10.33073/pjm-2020-035 Marine Sediment Recovered Salinispora sp. Inhibits the Growth of Emerging Bacterial Pathogens and other Multi-Drug-Resistant Bacteria LUIS CONTRERAS-CASTRO1 , SERGIO MARTÍNEZ-GARCÍA1, JUAN C. CANCINO-DIAZ1 , LUIS A. MALDONADO2 , CLAUDIA J. HERNÁNDEZ-GUERRERO3 , SERGIO F. MARTÍNEZ-DÍAZ3 , BÁRBARA GONZÁLEZ-ACOSTA3 and ERIKA T. QUINTANA1* 1 Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Ciudad de México, México 2 Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, México 3 Instituto Politécnico Nacional, Centro Interdisciplinario de Ciencias Marinas, Av. Instituto Politécnico Nacional S/N, Col. Playa Palo de Santa Rita, 23096, La Paz, Baja California Sur, México Submitted 19 March 2020, revised 22 July 2020, accepted 25 July 2020 Abstract Marine obligate actinobacteria produce a wide variety of secondary metabolites with biological activity, notably those with antibiotic activity urgently needed against multi-drug-resistant bacteria. Seventy-five marine actinobacteria were isolated from a marine sediment sample collected in Punta Arena de La Ventana, Baja California Sur, Mexico. The 16S rRNA gene identification, Multi Locus Sequence Analysis, and the marine salt requirement for growth assigned seventy-one isolates as members of the genus Salinispora, grouped apart but related to the main Salinispora arenicola species clade. The ability of salinisporae to inhibit bacterial growth of Staphylococcus epidermidis, Enterococ- cus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacer baumannii, Pseudomonas aeruginosa, and Enterobacter spp. was evaluated by cross-streaking plate and supernatant inhibition tests. Ten supernatants inhibited the growth of eight strains of S. -
Diversity and Evolution of Secondary Metabolism in the Marine
Diversity and evolution of secondary metabolism in the PNAS PLUS marine actinomycete genus Salinispora Nadine Ziemert, Anna Lechner, Matthias Wietz, Natalie Millán-Aguiñaga, Krystle L. Chavarria, and Paul Robert Jensen1 Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093 Edited* by Christopher T. Walsh, Harvard Medical School, Boston, MA, and approved February 6, 2014 (received for review December 30, 2013) Access to genome sequence data has challenged traditional natural The pathways responsible for secondary metabolite biosynthesis product discovery paradigms by revealing that the products of most are among the most rapidly evolving genetic elements known (5). bacterial biosynthetic pathways have yet to be discovered. Despite It has been shown that gene duplication, loss, and HGT have all the insight afforded by this technology, little is known about the played important roles in the distribution of PKSs among diversity and distributions of natural product biosynthetic pathways microbes (8, 9). Changes within PKS and NRPS genes also include among bacteria and how they evolve to generate structural di- mutation, domain rearrangement, and module duplication (5), all versity. Here we analyze genome sequence data derived from 75 of which can account for the generation of new small-molecule strains of the marine actinomycete genus Salinispora for pathways diversity. The evolutionary histories of specific PKS and NRPS associated with polyketide and nonribosomal peptide biosynthesis, domains have proven particularly informative, with KS and C the products of which account for some of today’s most important domains providing insight into enzyme architecture and function medicines. -
Phylogenetic Analysis of the Salinipostin Γ-Butyrolactone Gene
bioRxiv preprint doi: https://doi.org/10.1101/2020.10.16.342204; this version posted October 16, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Phylogenetic analysis of the salinipostin g-butyrolactone gene cluster uncovers 2 new potential for bacterial signaling-molecule diversity 3 4 Kaitlin E. Creamera, Yuta Kudoa, Bradley S. Mooreb,c, Paul R. Jensena# 5 6 a Center for Marine Biotechnology and Biomedicine, Scripps Institution of 7 Oceanography, University of California San Diego, La Jolla, California, USA 8 b Center for Oceans and Human Health, Scripps Institution of Oceanography, University 9 of California San Diego, La Jolla, California, USA 10 c Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California 11 San Diego, La Jolla, California, USA 12 13 Running Head: Phylogenetic analysis of the salinipostin gene cluster 14 15 #Address correspondence to Paul R. Jensen, [email protected]. 16 17 Keywords salinipostin, g-butyrolactones, biosynthetic gene clusters, Salinispora, 18 bacterial signaling molecules, actinomycetes, HGT bioRxiv preprint doi: https://doi.org/10.1101/2020.10.16.342204; this version posted October 16, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 19 Abstract 20 Bacteria communicate by small-molecule chemicals that facilitate intra- and inter- 21 species interactions. These extracellular signaling molecules mediate diverse processes 22 including virulence, bioluminescence, biofilm formation, motility, and specialized 23 metabolism. The signaling molecules produced by members of the phylum 24 Actinobacteria are generally comprised of g-butyrolactones, g-butenolides, and furans. -
Marine Natural Products: a Source of Novel Anticancer Drugs
marine drugs Review Marine Natural Products: A Source of Novel Anticancer Drugs Shaden A. M. Khalifa 1,2, Nizar Elias 3, Mohamed A. Farag 4,5, Lei Chen 6, Aamer Saeed 7 , Mohamed-Elamir F. Hegazy 8,9, Moustafa S. Moustafa 10, Aida Abd El-Wahed 10, Saleh M. Al-Mousawi 10, Syed G. Musharraf 11, Fang-Rong Chang 12 , Arihiro Iwasaki 13 , Kiyotake Suenaga 13 , Muaaz Alajlani 14,15, Ulf Göransson 15 and Hesham R. El-Seedi 15,16,17,18,* 1 Clinical Research Centre, Karolinska University Hospital, Novum, 14157 Huddinge, Stockholm, Sweden 2 Department of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, SE 106 91 Stockholm, Sweden 3 Department of Laboratory Medicine, Faculty of Medicine, University of Kalamoon, P.O. Box 222 Dayr Atiyah, Syria 4 Pharmacognosy Department, College of Pharmacy, Cairo University, Kasr el Aini St., P.B. 11562 Cairo, Egypt 5 Department of Chemistry, School of Sciences & Engineering, The American University in Cairo, 11835 New Cairo, Egypt 6 College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China 7 Department of Chemitry, Quaid-i-Azam University, Islamabad 45320, Pakistan 8 Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudingerweg 5, 55128 Mainz, Germany 9 Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, 12622 Giza, Egypt 10 Department of Chemistry, Faculty of Science, University of Kuwait, 13060 Safat, Kuwait 11 H.E.J. Research Institute of Chemistry, -
Genome Sequencing Reveals Complex Secondary Metabolome in the Marine Actinomycete Salinispora Tropica
Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica Daniel W. Udwary*, Lisa Zeigler*, Ratnakar N. Asolkar*, Vasanth Singan†, Alla Lapidus†, William Fenical*, Paul R. Jensen*, and Bradley S. Moore*‡§ *Scripps Institution of Oceanography and ‡Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093-0204; and †Department of Energy, Joint Genome Institute–Lawrence Berkeley National Laboratory, Walnut Creek, CA 94598 Edited by Christopher T. Walsh, Harvard Medical School, Boston, MA, and approved May 7, 2007 (received for review February 1, 2007) Recent fermentation studies have identified actinomycetes of the The biosynthetic genes responsible for the production of these marine-dwelling genus Salinispora as prolific natural product pro- metabolites are almost invariably tightly packaged into operon-like ducers. To further evaluate their biosynthetic potential, we se- clusters that include regulatory elements and resistance mecha- quenced the 5,183,331-bp S. tropica CNB-440 circular genome and nisms (11). In the case of modular polyketide synthase (PKS) and analyzed all identifiable secondary natural product gene clusters. nonribosomal peptide synthetase (NRPS) systems, the repetitive Our analysis shows that S. tropica dedicates a large percentage of domain structures associated with these megasynthases generally its genome (Ϸ9.9%) to natural product assembly, which is greater follow a colinearity rule (12) that, when combined with bio- than previous Streptomyces genome sequences as well as other informatics and biosynthetic precedence, can be used to predict natural product-producing actinomycetes. The S. tropica genome the chemical structures of new polyketide and peptide-based features polyketide synthase systems of every known formally metabolites. -
WO 2017/223239 Al 28 December 2017 (28.12.2017) W !P O PCT
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2017/223239 Al 28 December 2017 (28.12.2017) W !P O PCT (51) International Patent Classification: Published: A61K 31/445 (2006.01) C07D 471/04 (2006.01) — with international search report (Art. 21(3)) A61K 31/437 {2006.01) — before the expiration of the time limit for amending the (21) International Application Number: claims and to be republished in the event of receipt of PCT/US20 17/038609 amendments (Rule 48.2(h)) (22) International Filing Date: 2 1 June 2017 (21 .06.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/352,820 2 1 June 2016 (21 .06.2016) 62/456,526 08 February 2017 (08.02.2017) (71) Applicant: X4 PHARMACEUTICALS, INC. [US/US]; 955 Massachusetts Avenue; 4th Floor, Cambridge, Massa chusetts 02139 (US). (72) Inventors: BOURQUE, Elyse Marie Josee; 3115 Racine Street, Unit 214, Bellingham, Washington 98226 (US). SK- ERLJ, Renato; 12 Crocker Circle, West Newton, Massa chusetts 02465 (US). (74) Agent: REID, Andrea L., C. et al; One International Place, 40th Floor, 100 Oliver Street, Boston, Massachusetts 021 10-2605 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. -
Complex Evolutionary Dynamics Govern the Diversity and Distribution of Biosynthetic Gene Clusters and Their Encoded Specialized Metabolites
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.19.423547; this version posted December 20, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Complex evolutionary dynamics govern the diversity and distribution of biosynthetic gene clusters and their encoded specialized metabolites Alexander B. Chase1, Douglas Sweeney1,2, Mitchell N. Muskat1, Dulce Guillén-Matus1,2, and Paul R. Jensen1,2 1Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, California 2Marine Biology Research Division, Scripps Institution of Oceanography, University of California, San Diego, California ABSTRACT While specialized metabolites are thought to mediate ecological interactions, the evolutionary processes driving their distributions, particularly among closely related lineages, remain poorly understood. Here, we examine the evolutionary dynamics governing the diversity and distribution of biosynthetic gene clusters (BGCs) in 118 strains across nine described species within the marine actinomycete genus Salinispora. While previous evidence indicated that horizontal gene transfer largely contributed to BGC diversity, we find that a majority of BGCs in Salinispora genomes are maintained by processes of vertical descent. In particular, we identified species-specific signatures that were associated with both BGC distributions and the production of their encoded specialized metabolites. By analyzing nine experimentally characterized BGCs that range in conservation from species to genus specific, we find that the distribution of BGCs among Salinispora species is maintained by selection, while BGC diversification is constrained by recombination among closely related strains and strengthened by gain/loss events between species. -
Total Synthesis of Sporolide B
Kanai's Lab Literature Seminar (B4 part) Nov. 10th 2010 Junya Kawai (B4) Total Synthesis of Sporolide B Isolation: from Salinospora tropica (a marine actinomyceta), and it also produces salinosporamide A, a potent inhibitor of the 20S proteasome. Structure: determined in 2005 (Fenical et al., Org. Lett., 2005, 7, 2731-2734) 7 rings, 10 stereogenic centers, and 22 out of 24 carbons are either oxygenated or sp2 hybridized. Including highly substituted indane system, a 1,4-dioxane ring, an epoxy cyclohexenone hemiacetal, and 13-membered macrolide moiety. Difference between sporolide A and B is only the location of chlorine atom on the benzenoid structure. Biological activity: None (but the precursor enediyne compound is considered to have an antitumor activity) Synthetic study: K. Gademann et al., Synthesis, 2010, 4, 631-642 (Biomimetic method) Total synthesis: K. C. Nicolaou et al., Angew. Chem. Int. Ed. 2009, 48, 3449-3453 (Sporolide B ) K. C. Nicolaou et al., J. Am. Chem. Soc. 2010, 132,11350-11363 (Sporolide B, 9-epi-sporolide B) Synthesis of sporolide A has never been reported. Contents 1. Biomimetic approach 1-1. Hypothetical biosynthesis of sporolides 1-2. Bergman cycloaromatization 1-3. Nucleophilic addition to p-benzyne 1-4. Gademann's synthetic study 2. Nicolaou's approach 2-1. Retrosynthetic analysis 2-2. Hetero [4+2] cycloaddition 2-3. Regioselective [2+2+2] cycloaddition 2-4. Model studies about cycloaddition 2-5. Total synthesis of sporolide B salinosporamide A Angew. Chem. Int. Ed., 2010, 49, 2 Chem. Soc. Rev., 2009, 38, 2993 1 1. Biomimetic approach Moore et al., PNAS, 2007, 104, 10376-10381 Moore et al., J. -
Phytoplankton Trigger the Production of Cryptic Metabolites in the Marine 2 Actinobacteria Salinispora Tropica
bioRxiv preprint doi: https://doi.org/10.1101/2020.05.18.103358; this version posted May 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 1 Phytoplankton trigger the production of cryptic metabolites in the marine 2 actinobacteria Salinispora tropica. 3 4 Audam Chhun1,#, Despoina Sousoni1, Maria del Mar Aguiló-Ferretjans2, Lijiang Song3, Christophe 5 Corre1,3,#, Joseph A. Christie-Oleza1,2,4,# 6 7 1 School of Life Sciences, University of Warwick, Coventry, UK 8 2 University of the Balearic Islands, Palma, Spain 9 3 Department of Chemistry, University of Warwick, Coventry, UK 10 4 IMEDEA (CSIC-UIB), Esporles, Spain 11 12 #Corresponding authors: [email protected], [email protected] and [email protected] 13 14 15 Abstract 16 Bacteria from the Actinomycete family are a remarkable source of natural products with 17 pharmaceutical potential. The discovery of novel molecules from these organisms is, 18 however, hindered because most of the biosynthetic gene clusters (BGCs) encoding these 19 secondary metabolites are cryptic or silent and are referred to as orphan BGCs. While co- 20 culture has proven to be a promising approach to unlock the biosynthetic potential of many 21 microorganisms by activating the expression of these orphan BGCs, it still remains an 22 underexplored technique. The marine actinobacteria Salinispora tropica, for instance, 23 produces valuable compounds such as the anti-cancer molecule salinosporamide A but half 24 of its putative BGCs are still orphan. -
Salinispora Pacifica Sp. Nov., an Actinomycete from Marine Sediments
Antonie van Leeuwenhoek DOI 10.1007/s10482-013-9886-4 ORIGINAL PAPER Salinispora pacifica sp. nov., an actinomycete from marine sediments Lina Ahmed • Paul R. Jensen • Kelle C. Freel • Ros Brown • Amanda L. Jones • Byung-Yong Kim • Michael Goodfellow Received: 8 December 2012 / Accepted: 18 January 2013 Ó Springer Science+Business Media Dordrecht 2013 Abstract A polyphasic analysis was carried out to Keywords Salinispora pacifica sp. nov. Á clarify the taxonomic status of four marine actinomy- Polyphasic taxonomy Á Obligate marine actinomycete Á cete strains that share a phylogenetic relationship and Marine sediments Á Fiji phenotypic characteristics with the genus Salinispora. These strains formed a distinct lineage within the Salinispora 16S rRNA and gyrB trees and were found Introduction to possess a range of phenotypic properties and DNA:DNA hybridization values that distinguished The genus Salinispora is among a small but growing them from the type strains of the two validly named number of actinomycete genera that have been species in this genus, Salinispora tropica (CNB-440T, reported from marine sources (Han et al. 2003;Yi ATCC BAA-916T) and Salinispora arenicola (CNH- et al. 2004; Maldonado et al. 2005; Tian et al. 2009). 643T, ATCC BAA-917T). The combined genotypic Unlike other marine-derived genera described to date, and phenotypic data support this conclusion. It is members fail to grow when seawater is replaced with proposed that the strains be designated as Salinispora deionized water in the growth medium. The genus is pacifica sp. nov., the type strain of which is CNR-114T currently composed of two species, Salinispora aren- (DSMZ YYYYT = KACC 17160T). -
UNIVERSITY of CALIFORNIA, SAN DIEGO The
UNIVERSITY OF CALIFORNIA, SAN DIEGO The Comparative Genomics of Salinispora and the Distribution and Abundance of Secondary Metabolite Genes in Marine Plankton A Dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Marine Biology by Kevin Matthew Penn Committee in charge: Paul R. Jensen, Chair Eric Allen Lin Chao Bradley Moore Brian Palenik Forest Rohwer 2012 Copyright Kevin Matthew Penn, 2012 All rights reserved The Dissertation of Kevin Matthew Penn is approved, and it is acceptable in quality and form for publication on microfilm and electronically: Chair University of California, San Diego 2012 iii DEDICATION I dedicate this dissertation to my Mom Gail Penn and my Father Lawrence Penn they deserve more credit then any person could imagine. They have supported me through the good times and the bad times. They have never given up on me and they are always excited to know that I am doing well. They just want the best for me. They have encouraged my education from both a philosophical and financial point of view. I also thank my sister Heather Kalish and brother in-law Michael Kalish for providing me with support during the beginning of my academic career and introducing me to Jonathan Eisen who ended opening the door for me to an endless bounty of intellectual pursuits. iv EPIGRAPH “Nothing in Biology Makes Sense Except in the Light of Evolution” - Theodosius Dobzhansky, 1973 v TABLE OF CONTENTS SIGNATURE PAGE ..................................................................................................................................III -
Metagenomics and Metatranscriptomics of Lake Erie Ice
METAGENOMICS AND METATRANSCRIPTOMICS OF LAKE ERIE ICE Opeoluwa F. Iwaloye A Thesis Submitted to the Graduate College of Bowling Green State University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE August 2021 Committee: Scott Rogers, Advisor Paul Morris Vipaporn Phuntumart © 2021 Opeoluwa Iwaloye All Rights Reserved iii ABSTRACT Scott Rogers, Lake Erie is one of the five Laurentian Great Lakes, that includes three basins. The central basin is the largest, with a mean volume of 305 km2, covering an area of 16,138 km2. The ice used for this research was collected from the central basin in the winter of 2010. DNA and RNA were extracted from this ice. cDNA was synthesized from the extracted RNA, followed by the ligation of EcoRI (NotI) adapters onto the ends of the nucleic acids. These were subjected to fractionation, and the resulting nucleic acids were amplified by PCR with EcoRI (NotI) primers. The resulting amplified nucleic acids were subject to PCR amplification using 454 primers, and then were sequenced. The sequences were analyzed using BLAST, and taxonomic affiliations were determined. Information about the taxonomic affiliations, important metabolic capabilities, habitat, and special functions were compiled. With a watershed of 78,000 km2, Lake Erie is used for agricultural, forest, recreational, transportation, and industrial purposes. Among the five great lakes, it has the largest input from human activities, has a long history of eutrophication, and serves as a water source for millions of people. These anthropogenic activities have significant influences on the biological community. Multiple studies have found diverse microbial communities in Lake Erie water and sediments, including large numbers of species from the Verrucomicrobia, Proteobacteria, Bacteroidetes, and Cyanobacteria, as well as a diverse set of eukaryotic taxa.