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Title: A SHOTGUN METAGENOMIC APPROACH TO THE BIOSYNTHESIS OF MARINE NATURAL PRODUCTS.
Creator: Miller-Xavier, René Kathleen, Mincer, Tracy, Florida Atlantic University, Department of Biological Sciences, Charles E. Schmidt College of Science
Abstract/Description: Genomics has been revolutionized by improved sequencing technologies, allowing for the detailed exploration of microbial dark matter and complex microscopic ecosystems. The bottleneck in genomic workflows has shifted from high-throughput sequencing to data analysis. This dissertation developed the Florida Center for Coastal and Human Health Shotgun Metagenomics Workflow (FCHsm) that is easy to use and tailor to unique datasets. This work acts as the beta-testing for the workflow, as it...
Show moreGenomics has been revolutionized by improved sequencing technologies, allowing for the detailed exploration of microbial dark matter and complex microscopic ecosystems. The bottleneck in genomic workflows has shifted from high-throughput sequencing to data analysis. This dissertation developed the Florida Center for Coastal and Human Health Shotgun Metagenomics Workflow (FCHsm) that is easy to use and tailor to unique datasets. This work acts as the beta-testing for the workflow, as it analyzes disparate biomes (environmental and host microbiomes) at varying sequencing depths (shallow and deep). FCHsm was used to resolve molecular dynamics and mine trans-kingdom metagenomes for secondary metabolic biosynthetic gene clusters (BGCs) in two marine environments— Indian River Lagoon toxic harmful algal blooms (IRL HABs) and the medicinal Leiodermatium sponge holobiont. First, an in silico mock dataset was analyzed to benchmark the FCHsm workflow. Sourmash, coupled with the Genome Taxonomy Database, outcompeted the other taxonomic profilers by accurately predicting the size of the mock metagenome (450 genomes) and recalling the highest number of species (82 %) and strains (44 %). Nonpareil calculated the sequencing effort needed for 100 % coverage for all the datasets and correctly estimated the 75 Gbp of sequencing needed for almost 100 % coverage of the mock metagenomes (99.5 %). Next, the trans-kingdom metagenomes of the IRL were explored, and potential HAB biomarkers were identified.
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Date Issued: 2023
PURL: http://purl.flvc.org/fau/fd/FA00014186
Subject Headings: Marine natural products, Metagenomics
Format: Document (PDF)

Title: ESTABLISHING A SPONGE HYBRIDOMA FOR THE IN VITRO PRODUCTION OF A MARINE NATURAL PRODUCT.
Creator: Dougan, Cassady, Pomponi, Shirley A., Florida Atlantic University, Department of Marine Science and Oceanography, Charles E. Schmidt College of Science
Abstract/Description: Marine sponges are one of the most prolific sources of chemical compounds with pharmaceutical importance. To establish a supply of such compounds large enough for clinical development, in vitro production methodology was investigated. Since all sponge cells do not divide in culture, it was hypothesized that the fusion of rapidly dividing cells of a sponge that does not produce any compounds of interest with cells of a nondividing but compound-producing sponge would result in a hybridoma that...
Show moreMarine sponges are one of the most prolific sources of chemical compounds with pharmaceutical importance. To establish a supply of such compounds large enough for clinical development, in vitro production methodology was investigated. Since all sponge cells do not divide in culture, it was hypothesized that the fusion of rapidly dividing cells of a sponge that does not produce any compounds of interest with cells of a nondividing but compound-producing sponge would result in a hybridoma that produces the compound of interest. In this study, hybridomas have been produced with cells of two marine sponges, Axinella corrugata, which produces the antitumor compound stevensine, and Geodia neptuni, which divides rapidly in a nutrient medium optimized for sponge cell culture. Successful hybridization and subsequent cell division and in vitro stevensine production may unlock the potential for sustainable mass production of other sponge-derived compounds.
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Date Issued: 2022
PURL: http://purl.flvc.org/fau/fd/FA00014024
Subject Headings: Marine natural products, Sponges, Hybridomas, In vitro
Format: Document (PDF)

Title: Isolation and Biomimetic Synthesis of Marine Natural Products from the Gorgonian Briareum Asbestinum.
Creator: Simpson, Johnathon, West, Lyndon M., Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
Abstract/Description: Throughout history, natural products have produced a plethora of biologically active compounds that have established applications in medicine, biology, and pharmacy. The exploration for improved cytotoxic agents has continued to be a crucial path in natural products drug discovery. The focal point of this thesis sheds light on the biosynthetic relationship between the two distinct classes of briarane diterpenoids, the γ-lactone briarane and the briareolate esters. Additionally, this study...
Show moreThroughout history, natural products have produced a plethora of biologically active compounds that have established applications in medicine, biology, and pharmacy. The exploration for improved cytotoxic agents has continued to be a crucial path in natural products drug discovery. The focal point of this thesis sheds light on the biosynthetic relationship between the two distinct classes of briarane diterpenoids, the γ-lactone briarane and the briareolate esters. Additionally, this study elaborates on the discovery and elucidation of structurally unique secondary metabolites from the gorgonian coral Briareum asbestinum. The first chapter of this thesis provides a review of the development and discovery of diverse secondary metabolites. In addition, this chapter describes the role of natural products in drug discovery and summarizes the research progress in marine natural product chemistry in conjunction with a detailed overview of the current marine-derived pharmaceuticals.
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Date Issued: 2021
PURL: http://purl.flvc.org/fau/fd/FA00013857
Subject Headings: Marine natural products, Diterpenoids, Biomimetics, Soft corals
Format: Document (PDF)

Title: Discovery and investigation of survivin-targeting marine natural products from Ellisella paraplexauroides and Eudistoma olivaceum.
Creator: Francis, Kirstie Tandberg, Wright, Amy E., Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
Abstract/Description: In 2020, the National Institute of Health reported that more than 1.8 million people in the U.S. were diagnosed with cancer and over half a million died from those diseases. There is an urgent need for innovative and effective new treatments which stem from novel cancer drug targets. Survivin, the smallest member of the inhibitor of apoptosis protein (IAP) family, is highly expressed during development and in cancer cells but not in differentiated tissues, making it a tumor-selective target...
Show moreIn 2020, the National Institute of Health reported that more than 1.8 million people in the U.S. were diagnosed with cancer and over half a million died from those diseases. There is an urgent need for innovative and effective new treatments which stem from novel cancer drug targets. Survivin, the smallest member of the inhibitor of apoptosis protein (IAP) family, is highly expressed during development and in cancer cells but not in differentiated tissues, making it a tumor-selective target for new drug therapies. At only 16.5 kDa, it consists of a single Baculovirus IAP Repeat (BIR) domain and an α-helical coiled coil. Survivin plays a multitude of roles in the growth and survival of cancer cells—which can be attributed to the variable cellular localizations and posttranslational modifications of the protein—including inhibition of apoptosis, mitosis and cell cycle progression, DNA damage repair, drug resistance, metastasis, angiogenesis, and cell senescence, among others. A drug that is able to target surviving transcription or posttranslational modification or disrupt one of these critical pathways may serve as an attractive new cancer therapy. Despite decades of research on surviving and its intracellular functions, researchers have yet to find an FDA approved drug. Using a high throughput approach, Harbor Branch Oceanographic Institute’s chemical library of marine natural products was screened by the Guzmán lab to identify compounds capable of downregulating survivin expression in A549 non-small cell lung carcinoma and DLD-1 colorectal adenocarcinoma cell lines. From the screening assay, pure compounds were identified which reduce levels of survivin protein in cancer cells. Chapter 2 describes the isolation and structure elucidation of five polyhydroxylated sterol analogs from Ellisella paraplexauroides, four of them novel. Chapter 3 describes the isolation and structure elucidation of two compounds from Eudistoma olivaceum, eudistomin H and I. Chapter 4 describes the secondary biological testing employed to determine if the reduction of survivin expression was driven by reducing de novo production or increasing the degradation of existing protein by evaluating differential gene expression of survivin mRNA using reverse transcriptase quantitative polymerase chain reaction and measuring degradation rates of survivin protein, respectively.
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Date Issued: 2021
PURL: http://purl.flvc.org/fau/fd/FA00013828
Subject Headings: Survivin, Marine natural products, Antineoplastic agents--Development
Format: Document (PDF)

Title: CULTIVATION OF MICROBES ASSOCIATED WITH INDIAN RIVER LAGOON SPONGES.
Creator: Burton, Miranda Nicole, McCarthy, Peter, Florida Atlantic University, Department of Marine Science and Oceanography, Charles E. Schmidt College of Science
Abstract/Description: Cultivation of microbial populations is a necessity for the use of microbes within the biotechnological and pharmaceutical industries, however, approximately only 1% of bacteria have been successfully cultivated in the lab. Dilution to Extinction (DTE) is a technique which involves serially diluting a microbial suspension to single cell inoculum prior to inoculation in a liquid medium designed to replicate natural aquatic environments. This technique was used here for the cultivation of...
Show moreCultivation of microbial populations is a necessity for the use of microbes within the biotechnological and pharmaceutical industries, however, approximately only 1% of bacteria have been successfully cultivated in the lab. Dilution to Extinction (DTE) is a technique which involves serially diluting a microbial suspension to single cell inoculum prior to inoculation in a liquid medium designed to replicate natural aquatic environments. This technique was used here for the cultivation of diverse, potentially novel microbes from the marine sponge, Mycale microsigmatosa. One hundred thirty-six samples were successfully sequenced and identified with the majority belonging to the classes Alphaproteobacteria and Gammaproteobacteria. Furthermore, when combined with miniaturized fermentation, DTE allowed for the isolation and identification of marine natural products (3-Heptyl-3-hydroxy-2,4 (1H, 3H)-quinolinedione and 2-Heptyl-4-hydroxyquinoline) active against Methicillin-resistant Staphylococcus aureus. These metabolites originated from Pseudomonas aeruginosa, an isolate obtained from Mycale microsigmatosa using this technique.
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Date Issued: 2021
PURL: http://purl.flvc.org/fau/fd/FA00013858
Subject Headings: Indian River (Fla. : Lagoon), Sponges--Microbiology, Marine natural products
Format: Document (PDF)

Title: Isolation and Semi-synthesis of Marine Diterpenoids.
Creator: Scesa, Paul D., West, Lyndon, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
Abstract/Description: Natural products play a historical role in the discovery of medicine but present unique challenges for chemical isolation, identification and production. In this work we describe the identification of twenty novel diterpenoids. These were isolated by use of chromatography, and the structures determined by spectroscopic methods, primarily 1D and 2D NMR. Six of these possess unprecedented diterpenoid skeletons and two of them show significant growth inhibitory effects on cancer cell lines in...
Show moreNatural products play a historical role in the discovery of medicine but present unique challenges for chemical isolation, identification and production. In this work we describe the identification of twenty novel diterpenoids. These were isolated by use of chromatography, and the structures determined by spectroscopic methods, primarily 1D and 2D NMR. Six of these possess unprecedented diterpenoid skeletons and two of them show significant growth inhibitory effects on cancer cell lines in vitro (GI50 < 10 μM). The biomimetic semisynthesis of diterpendoids and analogues is also presented. Access to the bielschowskyane carbon skeleton by dearomatization of a furanocembranoid precursor is described. Highlights include a stereoselective alkene epoxidation, a novel kinetic furan dearomatization method, and an efficient [2+2] photochemical cycloaddition. The role of conformational steering was studied spectroscopically using VT 1H-NMR and NOESY as well as quantum chemical calculations at the DFT level of theory. We also disclose a biomimetic synthesis of providencin using a photochemical Norrish-Yang cyclization. This provided the absolute configuration by chemical correlation with the precursor bipinnatin E, the latter determined by x-ray diffraction. An unexpected, regioisomeric byproduct was observed and a possible mechanism is proposed. A biomimetic synthesis of the diterpene alkaloid aceropterine is also described, using an epoxidation-rearrangement cascade. This work led to a revised structure of aceropterine, formulated by spectroscopic methods. Finally, the isolation and structure elucidation of a novel, cyclic lipopeptide from Pseudomonas sp. is described. The compound was obtained using a unique antibiotic crowd sourcing approach and the structure determined by spectroscopic methods and advanced Marfey’s analysis.
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Date Issued: 2020
PURL: http://purl.flvc.org/fau/fd/FA00013539
Subject Headings: Marine natural products, Diterpenoids, Biomimetics
Format: Document (PDF)

Title: Isolation of briareolate esters from Briareum asbestinum.
Creator: Meginley, Rian J., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: The gorgonian Briareum asbestinum is widely studied because it possesses highly oxygenated novel structures, many of which exhibit useful biological activities. Recently, two new briarane diterpenoids, briareolate esters J and K, together with two known briareolate esters have been isolated from a specimen of Briareum asbestinum collected off the coast of Boca Raton, Florida. The method used was a 96-well plate real-time cell electronic sensing (RT-CES) system to discover compounds that...
Show moreThe gorgonian Briareum asbestinum is widely studied because it possesses highly oxygenated novel structures, many of which exhibit useful biological activities. Recently, two new briarane diterpenoids, briareolate esters J and K, together with two known briareolate esters have been isolated from a specimen of Briareum asbestinum collected off the coast of Boca Raton, Florida. The method used was a 96-well plate real-time cell electronic sensing (RT-CES) system to discover compounds that impact human embryonic stem cell growth. The compounds were isolated using reversed phase polystyrene divinylbenzene chromatographic support HP20ss followed by normal phased HPLC using a luna silica column. The structures of the compounds were established though the interpretation of spectroscopic data. Activity testing was conducted against hESCs (BG02) with briareolate ester J showing no inhibition activity and briareolate ester K showing mild activity with an EC50 value of 25 (So(BM. These results confirm that the exact confirmation and existence of the (E,Z)-dienone is related to the activity that was observed with the previously isolated briareolate esters L and M.
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Date Issued: 2013
PURL: http://purl.flvc.org/fcla/dt/3360959
Subject Headings: Coral reef ecology, Marine organisms, Environmental aspects, Marine natural products, Bioactive compounds
Format: Document (PDF)

Title: A novel activity from an old compound: Manzamine A reduces the metastatic potential of AsPC-1 pancreatic cancer cells and sensitizes them to TRAIL-induced apoptosis.
Creator: Guzman, Esther A., Johnson, J. D., Linley, P. A., Wright, Amy E., Gunasekera, Sarath P.
Date Issued: 2010
PURL: http://purl.flvc.org/FCLA/DT/3318907
Subject Headings: Pancreas--Cancer, Apoptosis, Sponges--Research, Marine natural products, Drug Discovery
Format: Document (PDF)

Title: Total synthesis of a library of designed hybrids of the microtubule-stabilising anticancer agents taxol, discodermolide and dictyostatin.
Creator: Paterson, Ian, Naylor, G. J., Fujita, T., Guzman, Esther A., Wright, Amy E.
Date Issued: 2010
PURL: http://purl.flvc.org/fau/fd/FA00007065
Subject Headings: Antineoplastic agents, Paclitaxel, Polyketides, Microtubules, Tubulin Modulators, Marine natural products
Format: Document (PDF)

Title: Gymnochromes E and F, cytotoxic phenanthroperylenequinones from a deep-water crinoid, Holopus rangii.
Creator: Wangun, H. V. K., Wood, A., Fiorilla, C., Reed, John K., McCarthy, Peter J., Wright, Amy E.
Date Issued: 2010
PURL: http://purl.flvc.org/FCLA/DT/3319112
Subject Headings: Crinoidea, Marine natural products, Cytotoxin, Marine metabolites, Anthraquinones
Format: Document (PDF)

Title: The Lithistida: important sources of compounds useful in biomedical research.
Creator: Wright, Amy E.
Date Issued: 2010
PURL: http://purl.flvc.org/FCLA/DT/3331940
Subject Headings: Sponges, Biomedical research, Marine natural products, Bioactive compounds
Format: Document (PDF)

Title: Isolation, synthesis, and biological activity of Aphrocallistin, an adenine-substituted bromotyramine metabolite from the hexactinellida sponge Aphrocallistes beatrix.
Creator: Wright, Amy E., Roth, G. P., Hoffman, J. K., Divlianska, D. B., Pechter, D., Sennett, Susan H., Guzman, Esther A., Linley, P. A., McCarthy, Peter J., Pitts, Tara P., Pomponi, Shirley A., Reed, John K.
Date Issued: 2009
PURL: http://purl.flvc.org/FCLA/DT/3319109
Subject Headings: Sponges --Research, Marine metabolites, Marine natural products, Hexactinellida
Format: Document (PDF)

Title: Selective cytotoxic activity of the marine derivedbatzelline compounds against pancreatic cancer cell lines.
Creator: Guzman, Esther A., Johnson, J. D., Carrier, M. K., Meyer, C. I., Pitts, Tara P., Gunasekera, Sarath P., Wright, Amy E.
Date Issued: 2009
PURL: http://purl.flvc.org/fau/fd/FA00007114
Subject Headings: Pancreas--Cancer, Marine natural products, Drug Discovery, Sponges--Caribbean Sea, Mechanism of action (Biochemistry)
Format: Document (PDF)

Title: Total synthesis of a potent hybrid of the anticancer natural products dictyostatin and discodermolide.
Creator: Paterson, Ian, Naylor, G. J., Wright, Amy E.
Date Issued: 2008
PURL: http://purl.flvc.org/fau/fd/FA00007062
Subject Headings: Antineoplastic agents, Macrolides, Polyketides, Tubulin Modulators, Marine natural products, Sponges
Format: Document (PDF)

Title: Neopeltolide a new macrolide from a lithistid sponge of the family Neopeltidae.
Creator: Wright, Amy E., Botelho, J. C., Guzman, Esther A., Harmody, Dedra K., Linley, P. A., McCarthy, Peter J., Pitts, Tara P., Pomponi, Shirley A., Reed, John K.
Date Issued: 2007
PURL: http://purl.flvc.org/FCLA/DT/3333011
Subject Headings: Sponges, Macrolides, Marine natural products
Format: Document (PDF)

Title: Marine biotechnology: realizing the potential.
Creator: Pomponi, Shirley A., Baden, Daniel G., Zohar, Y.
Date Issued: 2007
PURL: http://purl.flvc.org/FCLA/DT/3338530
Subject Headings: Marine biotechnology, Marine pharmacology, Marine natural products
Format: Document (PDF)

Title: A new sesterterpene, Sch 599473, from a marine sponge, Ircinia sp.
Creator: Yang, Shu-Wei, Chan, Tze-Ming, Pomponi, Shirley A., Gonsiorek, W., Chen, Guodong, Wright, Amy E., Hipkin, W., Patel, Mahesh, Gullo, Vincent, Pramanik, B., Zavodny, P., Chu, Min
Date Issued: 2003
PURL: http://purl.flvc.org/FCLA/DT/3351980
Subject Headings: Sponges, Sesterterpenes, Marine natural products
Format: Document (PDF)

Title: Five new Discodermolide analogues from the marine sponge Discodermia species.
Creator: Gunasekera, Sarath P., Paul, Gopal K., Longley, Ross E., Isbrucker, Richard A., Pomponi, Shirley A.
Date Issued: 2002
PURL: http://purl.flvc.org/FCLA/DT/3319106
Subject Headings: Sponges --Research, Cytotoxin, Marine natural products, Polyketides
Format: Document (PDF)

Title: Three new peroxides from the sponge Plakinastrella species.
Creator: Chen, Ying, Killday, K. B., McCarthy, Peter J., Schimoler, Rebecca, Chilson, Katherine, Selitrennikoff, Claude, Pomponi, Shirley A., Wright, Amy E.
Date Issued: 2001
PURL: http://purl.flvc.org/FCLA/DT/3319103
Subject Headings: Sponges --Research, Spectral analysis, Marine natural products, Peroxides, Antifungal agents
Format: Document (PDF)

Title: Acetylated analogues of the microtubule stabilizing agent Discodermolide: preparation and biological activity.
Creator: Gunasekera, Sarath P., Longley, Ross E., Isbrucker, Richard A., Harbor Branch Oceanographic Institute
Date Issued: 2001
PURL: http://purl.flvc.org/FCLA/DT/3319101
Subject Headings: Sponges --Research, Marine natural products, Cytotoxin, Acetylation
Format: Document (PDF)

HBOI Faculty Contributions (76)	+ -
FAU Theses and Dissertations (7)	+ -
HBOI Technical Reports (1)	+ -

Sponges (30)	+ -
Sponges --Research (25)	+ -
Cytotoxin (10)	+ -
Antineoplastic agents (9)	+ -
Bioactive compounds (9)	+ -

Marine metabolites (8)	+ -
Sesquiterpenes (7)	+ -
Macrolides (5)	+ -
Polyketides (5)	+ -
Alkaloids (4)	+ -
Antifungal agents (4)	+ -
Drug Discovery (4)	+ -
Immunosuppressive agents (4)	+ -
Marine organisms (4)	+ -
Indole alkaloids (3)	+ -
Marine pharmacology (3)	+ -
Paclitaxel (3)	+ -
Pancreas--Cancer (3)	+ -
Sterols (3)	+ -
Tubulin Modulators (3)	+ -
Antitumor agents (2)	+ -
Antiviral agents (2)	+ -
Biomedical Research (2)	+ -
Biomedical research (2)	+ -
Biomimetics (2)	+ -
Chemical structure (2)	+ -
Cytotoxins (2)	+ -
Diterpenoids (2)	+ -
Drug development (2)	+ -

article (76)	+ -
Electronic Thesis or Dissertation (7)	+ -
technical report (1)	+ -

Wright, Amy E. (32)	+ -
Harbor Branch Oceanographic Institute (28)	+ -
Pomponi, Shirley A. (28)	+ -
Gunasekera, Sarath P. (19)	+ -
Kelly-Borges, M. (18)	+ -

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