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Biologically Active Compounds from Pacific Tunicates;
BIOLOGICALLY ACTIVE COMPOUNDS FROM PACIFIC TUNICATES by David Francis Sesin A dissertation submitted to the faculty of The University of Utah in partial fulfillment of the requirements for the degree of Doctor of Philosophy Department of Medicinal Chemistry The University of Utah December 1986 View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by The University of Utah: J. Willard Marriott Digital Library THE UNIVERSITY OF UTAH GRADUATE SCHOOL SUPERVISORY COMMITTEE APPROVAL of a dissertation submitted by DAVID FRANCIS SESIN This dissertation has been read by each member of the following supervisory committee and by majority vote has been found to be satisfactory .. September 16. 1986 Chainnan:chris M. Ire'iand. Ph.D. September 16. 1986 Arthur D. Broom. Ph.D. September 16. 1986 ark E. Sanders. Ph.D. September 16, 1986 Martin P. Schweizer.�.D. September 16. 1986 David M. Grant. Ph.D. THE VI'IiIVERSITY OF UTAH GRADUATE SCHOOL FINAL READING APPRC)VAL To the Graduate Council of The University of Utah: I have read the dissertation of David Francis Sesin 10 Its final form and have found that (I) its format. citations. and bibliographic style are consistent and acceptable; (2) its illustrative materials including figures. tables. and charts are in place: and (3) the final manuscript is satisfactory to the Supervis ory Committee and is ready for submission to the Graduate School. Date Chris M. Ireland. Ph.D. Chairp(,rson. Supt'rvisory Commill('t, Approved for the Major Departmenl Arthur D. Broom. Ph.D. Chairman / Dean Approved ror lhe GradU,Ill' Coullcil Dean of The (;raduate Sdl()ol Copyright@ David Francis Sesin 1986 All Rights Reserved ABSTRACT Tunicates have proven to be a rich source of structurally-diverse metabolites covering a broad spectrum of biological activities. -
Sea Squirt Symbionts! Or What I Did on My Summer Vacation… Leah Blasiak 2011 Microbial Diversity Course
Sea Squirt Symbionts! Or what I did on my summer vacation… Leah Blasiak 2011 Microbial Diversity Course Abstract Microbial symbionts of tunicates (sea squirts) have been recognized for their capacity to produce novel bioactive compounds. However, little is known about most tunicate-associated microbial communities, even in the embryology model organism Ciona intestinalis. In this project I explored 3 local tunicate species (Ciona intestinalis, Molgula manhattensis, and Didemnum vexillum) to identify potential symbiotic bacteria. Tunicate-specific bacterial communities were observed for all three species and their tissue specific location was determined by CARD-FISH. Introduction Tunicates and other marine invertebrates are prolific sources of novel natural products for drug discovery (reviewed in Blunt, 2010). Many of these compounds are biosynthesized by a microbial symbiont of the animal, rather than produced by the animal itself (Schmidt, 2010). For example, the anti-cancer drug patellamide, originally isolated from the colonial ascidian Lissoclinum patella, is now known to be produced by an obligate cyanobacterial symbiont, Prochloron didemni (Schmidt, 2005). Research on such microbial symbionts has focused on their potential for overcoming the “supply problem.” Chemical synthesis of natural products is often challenging and expensive, and isolation of sufficient quantities of drug for clinical trials from wild sources may be impossible or environmentally costly. Culture of the microbial symbiont or heterologous expression of the biosynthetic genes offers a relatively economical solution. Although the microbial origin of many tunicate compounds is now well established, relatively little is known about the extent of such symbiotic associations in tunicates and their biological function. Tunicates (or sea squirts) present an interesting system in which to study bacterial/eukaryotic symbiosis as they are deep-branching members of the Phylum Chordata (Passamaneck, 2005 and Buchsbaum, 1948). -
Origins and Bioactivities of Natural Compounds Derived from Marine Ascidians and Their Symbionts
marine drugs Review Origins and Bioactivities of Natural Compounds Derived from Marine Ascidians and Their Symbionts Xiaoju Dou 1,4 and Bo Dong 1,2,3,* 1 Laboratory of Morphogenesis & Evolution, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China; [email protected] 2 Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China 3 Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China 4 College of Agricultural Science and Technology, Tibet Vocational Technical College, Lhasa 850030, China * Correspondence: [email protected]; Tel.: +86-0532-82032732 Received: 29 October 2019; Accepted: 25 November 2019; Published: 28 November 2019 Abstract: Marine ascidians are becoming important drug sources that provide abundant secondary metabolites with novel structures and high bioactivities. As one of the most chemically prolific marine animals, more than 1200 inspirational natural products, such as alkaloids, peptides, and polyketides, with intricate and novel chemical structures have been identified from ascidians. Some of them have been successfully developed as lead compounds or highly efficient drugs. Although numerous compounds that exist in ascidians have been structurally and functionally identified, their origins are not clear. Interestingly, growing evidence has shown that these natural products not only come from ascidians, but they also originate from symbiotic microbes. This review classifies the identified natural products from ascidians and the associated symbionts. Then, we discuss the diversity of ascidian symbiotic microbe communities, which synthesize diverse natural products that are beneficial for the hosts. Identification of the complex interactions between the symbiont and the host is a useful approach to discovering ways that direct the biosynthesis of novel bioactive compounds with pharmaceutical potentials. -
Patellamide a and C Biosynthesis by a Microcin-Like Pathway in Prochloron Didemni, the Cyanobacterial Symbiont of Lissoclinum Patella
Patellamide A and C biosynthesis by a microcin-like pathway in Prochloron didemni, the cyanobacterial symbiont of Lissoclinum patella Eric W. Schmidt*†, James T. Nelson*, David A. Rasko‡, Sebastian Sudek§, Jonathan A. Eisen‡, Margo G. Haygood§, and Jacques Ravel‡ *Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84112; ‡The Institute for Genomic Research, Rockville, MD 20850; and §Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA 92093 Edited by Robert Haselkorn, University of Chicago, Chicago, IL, and approved April 7, 2005 (received for review February 18, 2005) Prochloron spp. are obligate cyanobacterial symbionts of many a project to sequence the genome of Prochloron didemni, isolated didemnid family ascidians. It has been proposed that the cyclic from the ascidian Lissoclinum patella. peptides of the patellamide class found in didemnid extracts are The patellamides and trunkamide (another didemnid product) synthesized by Prochloron spp., but studies in which host and are peptides that exemplify both the unique structural features and symbiont cells are separated and chemically analyzed to identify potent bioactivities of didemnid ascidian natural products (Fig. 1). the biosynthetic source have yielded inconclusive results. As part Both groups have clinical potential, because patellamides are of the Prochloron didemni sequencing project, we identified pa- typically moderately cytotoxic, and patellamides B, C, and D tellamide biosynthetic genes and confirmed their function by reportedly reverse multidrug resistance (15, 16), whereas trunka- heterologous expression of the whole pathway in Escherichia coli. mide was initially isolated because of specific and unusual activity The primary sequence of patellamides A and C is encoded on a against the multidrug-resistant UO-31 renal cell line (17). -
Species Specificity of Symbiosis and Secondary Metabolism in Ascidians
The ISME Journal (2015) 9, 615–628 & 2015 International Society for Microbial Ecology All rights reserved 1751-7362/15 www.nature.com/ismej ORIGINAL ARTICLE Species specificity of symbiosis and secondary metabolism in ascidians Ma Diarey B Tianero1, Jason C Kwan1,2, Thomas P Wyche2, Angela P Presson3, Michael Koch4, Louis R Barrows4, Tim S Bugni2 and Eric W Schmidt1 1Department of Medicinal Chemistry, L.S. Skaggs Pharmacy Institute, University of Utah, Salt Lake City, UT, USA; 2School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA; 3Study Design and Biostatistics Center, Division of Epidemiology, University of Utah, Salt Lake City, UT, USA and 4Department of Pharmacology and Toxicology, L.S. Skaggs Pharmacy Institute, University of Utah, Salt Lake City, UT, USA Ascidians contain abundant, diverse secondary metabolites, which are thought to serve a defensive role and which have been applied to drug discovery. It is known that bacteria in symbiosis with ascidians produce several of these metabolites, but very little is known about factors governing these ‘chemical symbioses’. To examine this phenomenon across a wide geographical and species scale, we performed bacterial and chemical analyses of 32 different ascidians, mostly from the didemnid family from Florida, Southern California and a broad expanse of the tropical Pacific Ocean. Bacterial diversity analysis showed that ascidian microbiomes are highly diverse, and this diversity does not correlate with geographical location or latitude. Within a subset of species, ascidian microbiomes are also stable over time (R ¼À0.037, P-value ¼ 0.499). Ascidian microbiomes and metabolomes contain species-specific and location-specific components. Location-specific bacteria are found in low abundance in the ascidians and mostly represent strains that are widespread. -
And Transcriptomic-Profiling of the Host-Associated Cyanobacteria Prochloron and Acaryochloris Marina
The ISME Journal (2018) 12, 556–567 © 2018 International Society for Microbial Ecology All rights reserved 1751-7362/18 www.nature.com/ismej ORIGINAL ARTICLE In situ metabolomic- and transcriptomic-profiling of the host-associated cyanobacteria Prochloron and Acaryochloris marina Lars Behrendt1,2,3, Jean-Baptiste Raina4, Adrian Lutz5, Witold Kot6, Mads Albertsen7, Per Halkjær-Nielsen7, Søren J Sørensen3, Anthony WD Larkum4 and Michael Kühl2,4 1Department of Civil, Environmental and Geomatic Engineering, Swiss Federal Institute of Technology, Zürich, Switzerland; 2Marine Biological Section, Department of Biology, University of Copenhagen, Helsingør, Denmark; 3Microbiology Section, Department of Biology, University of Copenhagen, Copenhagen, Denmark; 4Plant Functional Biology and Climate Change Cluster (C3), University of Technology, Sydney, New South Wales, Australia; 5Metabolomics Australia, School of BioSciences, University of Melbourne, Parkville, Victoria, Australia; 6Department of Environmental Science—Enviromental Microbiology and Biotechnology, Aarhus University, Roskilde, Denmark and 7Center for Microbial Communities, Department of Chemistry and Bioscience, Aalborg University, Aalborg, Denmark The tropical ascidian Lissoclinum patella hosts two enigmatic cyanobacteria: (1) the photoendo- symbiont Prochloron spp., a producer of valuable bioactive compounds and (2) the chlorophyll-d containing Acaryochloris spp., residing in the near-infrared enriched underside of the animal. Despite numerous efforts, Prochloron remains uncultivable, -
A New Record of Photosymbiotic Ascidians from Andaman & Nicobar
Indian Journal of Geo Marine Sciences Vol.46 (11), November 2017, pp. 2393-2398 A new record of photosymbiotic ascidians from Andaman & Nicobar Islands, India Chinnathambi Stalin1, Gnanakkan Ananthan1* & Chelladurai Raghunathan2 1CAS in Marine Biology, Annamalai University, Parangipettai – 628 502, Tamil Nadu, India. 2Zoological Survey of India, Andaman and Nicobar Regional Centre, Port Blair – 744 102, India. [Email: [email protected]] Received 30 June 2015 ; revised 22 November 2016 Photosymbiotic ascidian fauna were surveyed in the intertidal and subtidal zone off Andaman and Nicobar Islands in India. A total of four species, Didemnum molle, Diplosoma simile, Lissoclinum patella and Trididemnum cyclops, were newly recorded in India. Clean waters in Andaman and Nicobar Islands probably provide a better environment for the growth of photosymbiotic ascidians and this area has a greater variety of these ascidians than the other areas in India and all of the observed species are potentially widely distributed in Coco-Channel, Andaman Sea, Great Channel and Bay of Bengal coral reefs. [Keywords: Photosymbiotic, Intertidal, Sub tidal, Islands, Coral reefs] Introduction Diplosoma simile (Sluiter, 1909), Lissoclinum A number of tropical species have patella (Gottscholdt, 1898) and Trididemnum obligate symbioses with chlorophyll-containing cyclops (Michaelsen, 1921) are widespread in cells. Supplementary tropical species at times Indian waters. Andaman and Nicobar Islands have have patches of non-obligate symbionts, a coastline of 900n km with 572 islands habitually Prochloron, on the surface1. This is an surrounded by Coco-Channel, Andaman Sea, exclusive symbiotic system from the viewpoints Great Channel and Bay of Bengal. The of evolution and ecology. Hence researchers of advantageous geographic position of this region biochemical and pharmaceutical science have also provides a compassionate atmosphere for a great paid particular attention to photosynthetic deal of marine organisms. -
Marine Natural Products from Tunicates and Their Associated Microbes
marine drugs Review Marine Natural Products from Tunicates and Their Associated Microbes Chatragadda Ramesh 1,2,*, Bhushan Rao Tulasi 3, Mohanraju Raju 2, Narsinh Thakur 4 and Laurent Dufossé 5,* 1 Biological Oceanography Division (BOD), CSIR-National Institute of Oceanography (CSIR-NIO), Dona Paula 403004, India 2 Department of Ocean Studies and Marine Biology, Pondicherry Central University, Brookshabad Campus, Port Blair 744102, India; [email protected] 3 Zoology Division, Sri Gurajada Appa Rao Government Degree College, Yellamanchili 531055, India; [email protected] 4 Chemical Oceanography Division (COD), CSIR-National Institute of Oceanography (CSIR-NIO), Dona Paula 403004, India; [email protected] 5 Laboratoire de Chimie et Biotechnologie des Produits Naturels (CHEMBIOPRO), Université de La Réunion, ESIROI Agroalimentaire, 15 Avenue René Cassin, CS 92003, CEDEX 9, F-97744 Saint-Denis, Ile de La Réunion, France * Correspondence: [email protected] (C.R.); [email protected] (L.D.); Tel.: +91-(0)-832-2450636 (C.R.); +33-668-731-906 (L.D.) Abstract: Marine tunicates are identified as a potential source of marine natural products (MNPs), demonstrating a wide range of biological properties, like antimicrobial and anticancer activities. The symbiotic relationship between tunicates and specific microbial groups has revealed the acquisi- tion of microbial compounds by tunicates for defensive purpose. For instance, yellow pigmented compounds, “tambjamines”, produced by the tunicate, Sigillina signifera (Sluiter, 1909), primarily Citation: Ramesh, C.; Tulasi, B.R.; originated from their bacterial symbionts, which are involved in their chemical defense function, indi- Raju, M.; Thakur, N.; Dufossé, L. cating the ecological role of symbiotic microbial association with tunicates. This review has garnered Marine Natural Products from comprehensive literature on MNPs produced by tunicates and their symbiotic microbionts. -
Bacterial Endosymbiosis in a Chordate Host: Long-Term Co-Evolution and Conservation of Secondary Metabolism
Bacterial Endosymbiosis in a Chordate Host: Long-Term Co-Evolution and Conservation of Secondary Metabolism Jason C. Kwan¤, Eric W. Schmidt* Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah, United States of America Abstract Intracellular symbiosis is known to be widespread in insects, but there are few described examples in other types of host. These symbionts carry out useful activities such as synthesizing nutrients and conferring resistance against adverse events such as parasitism. Such symbionts persist through host speciation events, being passed down through vertical transmission. Due to various evolutionary forces, symbionts go through a process of genome reduction, eventually resulting in tiny genomes where only those genes essential to immediate survival and those beneficial to the host remain. In the marine environment, invertebrates such as tunicates are known to harbor complex microbiomes implicated in the production of natural products that are toxic and probably serve a defensive function. Here, we show that the intracellular symbiont Candidatus Endolissoclinum faulkneri is a long-standing symbiont of the tunicate Lissoclinum patella, that has persisted through cryptic speciation of the host. In contrast to the known examples of insect symbionts, which tend to be either relatively recent or ancient relationships, the genome of Ca. E. faulkneri has a very low coding density but very few recognizable pseudogenes. The almost complete degradation of intergenic regions and stable gene inventory of extant strains of Ca. E. faulkneri show that further degradation and deletion is happening very slowly. This is a novel stage of genome reduction and provides insight into how tiny genomes are formed. -
An Elongated COI Fragment to Discriminate Botryllid Species And
www.nature.com/scientificreports OPEN An elongated COI fragment to discriminate botryllid species and as an improved ascidian DNA barcode Marika Salonna1, Fabio Gasparini2, Dorothée Huchon3,4, Federica Montesanto5, Michal Haddas‑Sasson3,4, Merrick Ekins6,7,8, Marissa McNamara6,7,8, Francesco Mastrototaro5,9 & Carmela Gissi1,9,10* Botryllids are colonial ascidians widely studied for their potential invasiveness and as model organisms, however the morphological description and discrimination of these species is very problematic, leading to frequent specimen misidentifcations. To facilitate species discrimination and detection of cryptic/new species, we developed new barcoding primers for the amplifcation of a COI fragment of about 860 bp (860‑COI), which is an extension of the common Folmer’s barcode region. Our 860‑COI was successfully amplifed in 177 worldwide‑sampled botryllid colonies. Combined with morphological analyses, 860‑COI allowed not only discriminating known species, but also identifying undescribed and cryptic species, resurrecting old species currently in synonymy, and proposing the assignment of clade D of the model organism Botryllus schlosseri to Botryllus renierii. Importantly, within clade A of B. schlosseri, 860‑COI recognized at least two candidate species against only one recognized by the Folmer’s fragment, underlining the need of further genetic investigations on this clade. This result also suggests that the 860‑COI could have a greater ability to diagnose cryptic/ new species than the Folmer’s fragment at very short evolutionary distances, such as those observed within clade A. Finally, our new primers simplify the amplifcation of 860‑COI even in non‑botryllid ascidians, suggesting their wider usefulness in ascidians. -
Ascidiacea Ascidiacea
ASCIDIACEA ASCIDIACEA The Ascidiacea, the largest class of the Tunicata, are fixed, filter feeding organisms found in most marine habitats from intertidal to hadal depths. The class contains two orders, the Enterogona in which the atrial cavity (atrium) develops from paired dorsal invaginations, and the Pleurogona in which it develops from a single median invagination. These ordinal characters are not present in adult organisms. Accordingly, the subordinal groupings, Aplousobranchia and Phlebobranchia (Enterogona) and Stolidobranchia (Pleurogona), are of more practical use at the higher taxon level. In the earliest classification (Savigny 1816; Milne-Edwards 1841) ascidians-including the known salps, doliolids and later (Huxley 1851), appendicularians-were subdivided according to their social organisation, namely, solitary and colonial forms, the latter with zooids either embedded (compound) or joined by basal stolons (social). Recognising the anomalies this classification created, Lahille (1886) used the branchial sacs to divide the group (now known as Tunicata) into three orders: Aplousobranchia (pharynx lacking both internal longitudinal vessels and folds), Phlebobranchia (pharynx with internal longitudinal vessels but lacking folds), and Stolidobranchia (pharynx with both internal longitudinal vessels and folds). Subsequently, with thaliaceans and appendicularians in their own separate classes, Lahille's suborders came to refer only to the Class Ascidiacea, and his definitions were amplified by consideration of the position of the gut and gonads relative to the branchial sac (Harant 1929). Kott (1969) recognised that the position of the gut and gonads are linked with the condition and function of the epicardium. These are significant characters and are informative of phylogenetic relationships. However, although generally conforming with Lahille's orders, the new phylogeny cannot be reconciled with a too rigid adherence to his definitions based solely on the branchial sac. -
Antimicrobial and Cytotoxic Properties of the Ascidians Lissoclinum
Original Article 65 Pharmaceutical Sciences and Research (PSR), 5(2), 2018, 65 - 71 Antimicrobial and Cytotoxic Properties of the Ascidians Lissoclinum patella, Oxycoryna fascicularis, Didemnum molle and Botryllus schlosseri Firmansyah Karim1, Masteria Yunovilsa Putra1, Tri Aryono Hadi1, Muhammad Abrar1 1Research Center for Oceanography, Indonesian Institute of Science ABSTRACT The aim of this research was to investigate antimicrobial and cytotoxic activity of Indonesian ascidians. Extracts prepared from the Indonesian ascidians namely Lissoclinum patella, Oxycoryna fascicularis, Didemnum molle and Botryllus schlosseri were assessed for anti- microbial and cytotoxic properties. Antibacterial activity of the extracts was tested against two Gram-positive bacteria, viz. Bacillus subtilis ATCC 6633 and Staphylococcus aureus ATCC 25923, and three Gram-negative bacteria, viz. Escherichia coli ATCC 25922, Vibrio cholerae ATCC 14035 and Pseudomonas aeruginosa ATCC 101454 using the disk ARTICLE HISTORY diffusion test. Antifungal activity was also tested againstCandida albicans ATCC 10231 and Received: October 2017 Aspergillus niger ATCC 16404. The minimum inhibitory concentrations (MICs) of potential Revised: November 2017 ascidian extracts were determined by the microdilution technique. Cytotoxicity of the extracts Accepted: June 2018 was assessed using the brine shrimp lethality bioassay. By comparing the inhibition zones in the disk diffusion test, the most active anti-bacterial activity against Gram-positive bacteria (S. aureus and B. subtilis) was found in the crude extracts of Oxycoryna fascicularis and Didemnum molle. Lissoclinum patella extract showed the highest activity against the Gram- negative bacteria E. coli and V. cholerae. The LC50 values of the crude extracts of Lissoclinum patella, Didemnum molle, Botryllus schlosseri, and Oxycoryna fascicularis were 74.3, 97.2, 114.7 and 132.9 μg/ml, respectively.