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9,11-secogorgosterol biosynthesis in gorgonians
Title
9,11-secogorgosterol biosynthesis in gorgonians.
Creator
Kellman, Jaelle, Florida Atlantic University, Kerr, Russell G., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description
9,11-secogorgosterol is a secondary metabolite from the gorgonian Pseudopterogorgia americana which acts as a chemical defense. The soft coral lives in a symbiotic association with unicellular algae known as zooxanthellae. A biosynthetic investigation, using in vivo and in vitro methods, has resulted in the identification of the metabolic precursor of 9,11-secogorgosterol as gorgosterol. This finding is significant as it indicates that the conversion of gorgosterol to 9,11-secogorgosterol is...
Show more9,11-secogorgosterol is a secondary metabolite from the gorgonian Pseudopterogorgia americana which acts as a chemical defense. The soft coral lives in a symbiotic association with unicellular algae known as zooxanthellae. A biosynthetic investigation, using in vivo and in vitro methods, has resulted in the identification of the metabolic precursor of 9,11-secogorgosterol as gorgosterol. This finding is significant as it indicates that the conversion of gorgosterol to 9,11-secogorgosterol is due to gorgonian metabolism. Since gorgosterol is known to be a product of zooxanthellae metabolism, this would be the first example of a defensive secondary metabolite being produced by two organisms living in symbiosis. A viable acetone powder has been generated from the crude cell-free extract and has demonstrated the efficient transformation of gorgosterol to 9, 11-secogorgosterol. This indicates possible future value as a synthetic tool for secosterol production.
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Date Issued
1995
PURL
http://purl.flvc.org/fcla/dt/15180
Subject Headings
Sterols--Synthesis, Alcyonacea
Format
Document (PDF)
biosynthetic production of marine-derived anti-tumor ecteinascidins and the aquaculture of the marine tunicate Ecteinascidia turbinata
Title
The biosynthetic production of marine-derived anti-tumor ecteinascidins and the aquaculture of the marine tunicate Ecteinascidia turbinata.
Creator
Krenisky, Joann Mary, Florida Atlantic University, Kerr, Russell G., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description
A family of tetrahydroisoquinoline alkaloids, the ecteinascidins, are a group of biologically active secondary metabolites produced by the marine tunicate Ecteinascidia turbinata. Ecteinascidins have shown in vivo anti-tumor activity against P388 lymphoma, B16 melanoma, M5076 ovarian sarcoma, Lewis lung carcinoma, and LX-1 human lung and MX-1 human mammary carcinoma xenografts in laboratory mice. Because ecteinascidins are produced in low yields, 1x10^-4%, supply for clinical development is a...
Show moreA family of tetrahydroisoquinoline alkaloids, the ecteinascidins, are a group of biologically active secondary metabolites produced by the marine tunicate Ecteinascidia turbinata. Ecteinascidins have shown in vivo anti-tumor activity against P388 lymphoma, B16 melanoma, M5076 ovarian sarcoma, Lewis lung carcinoma, and LX-1 human lung and MX-1 human mammary carcinoma xenografts in laboratory mice. Because ecteinascidins are produced in low yields, 1x10^-4%, supply for clinical development is a significant problem. The ultimate goal of this study is to develop an enzyme-based synthesis of the ecteinascidins. In this regard, the biosynthesis of these alkaloids has been investigated. Optimal conditions for in vitro ecteinascidin biosynthesis were found. The origin of the C22-C1 two-carbon unit was identified as pyruvate and the tyrosine and DOPA diketopiperazines were identified as key intermediates. Methods were developed for an in-the-sea aquaculture of the colonal marine ascidian Ecteinascidia turbinata.
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Date Issued
1997
PURL
http://purl.flvc.org/fcla/dt/15454
Subject Headings
Sea squirts, Tetrahydroisoquinolines, Alkaloids--Synthesis
Format
Document (PDF)
Biosynthetic Studies of the Bryostatins, Anticancer Agents from the Marine Bryozoan Bugu/a neritina
Title
Biosynthetic Studies of the Bryostatins, Anticancer Agents from the Marine Bryozoan Bugu/a neritina.
Creator
Lawry, Joseph, Kerr, Russell G., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description
The bryostatins are a family of macrolide lactones isolated from the marine bryozoan Bugu/a neritina. Since its detection in 1968, bryostatin 1 has demonstrated remarkable anticancer, immunopotentiating, biomodulatory and radioprotective effects which result mainly from its ability to activate protein kinase C, a family of isozymes involved in cellular signal transduction. It is currently being tested in several phase I and phase II clinical trials as a potential anticancer drug for leukemia,...
Show moreThe bryostatins are a family of macrolide lactones isolated from the marine bryozoan Bugu/a neritina. Since its detection in 1968, bryostatin 1 has demonstrated remarkable anticancer, immunopotentiating, biomodulatory and radioprotective effects which result mainly from its ability to activate protein kinase C, a family of isozymes involved in cellular signal transduction. It is currently being tested in several phase I and phase II clinical trials as a potential anticancer drug for leukemia, melanoma and nephrotoma. A series of experiments was undertaken to elucidate the biosynthetic origins of bryostatin, using a fortified crude cell-free enzyme preparation and radiolabelled precursors. A regional characterization of Bugula neritina from Sicily, Italy and Daytona Beach, Florida is also described.
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Date Issued
1997
PURL
http://purl.flvc.org/fau/fd/FA00000787
Subject Headings
Macrolide antibiotics, Bryozoa, Marine pharmacology
Format
Document (PDF)
Development of Methods for Separation and Characterization of Proteins from Gorgonian Sources
Title
Development of Methods for Separation and Characterization of Proteins from Gorgonian Sources.
Creator
Jett, Steven W., Florida Atlantic University, Kerr, Russell G., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description
Research into the chemical constituents of marine organisms is a relatively new and growing field, given that much of the marine environment has only in the last half century become accessible. Despite the strides that have been made in ocean exploration, the marine biome has still been only barely explored. Much of the impetus for the isolation and identification of chemical entities from marine organisms has been related to their potential as medicines. For a number of reasons, including...
Show moreResearch into the chemical constituents of marine organisms is a relatively new and growing field, given that much of the marine environment has only in the last half century become accessible. Despite the strides that have been made in ocean exploration, the marine biome has still been only barely explored. Much of the impetus for the isolation and identification of chemical entities from marine organisms has been related to their potential as medicines. For a number of reasons, including synthetic efficiency, this has meant that many marine compounds isolated and studied have been small molecules. In recent years, large strides have been made in techniques for the isolation and identification of biological macromolecules, especially proteins. The understanding of these molecules, and their relationship to the biochemical processes of the marine organisms from which they have been isolated, is important not only because of the potential for this information to help in the synthesis of medicines, but because it may help in the recognition of processes that affect the very viability of marine organisms increasingly exposed to anthropogenic threats to their environment. This work consists of four related studies involving the development of methods for the separation and identification of proteins from a number or gorgon ian species. Chromatographic and gel based methods were used to isolate an elisabethatriene synthase (ELS) which shows promise as a biotechnological tool for the production or pseudopterosins. A number of gorgonians were screened for the presence of proteins that might have antimicrobial properties, and several organisms were identified that might be of interest in this context. Two-dimensional gel electrophoresis methods were then developed to allow the construction of gel maps for the azooxanthellate gorgonian Leptogorgia minimata and the xoozanthellae gorgonian Pseudopterogorgia e/isahethae, the separated proteins were digested and analyzed by LC/MSMS. and the information generated was used to examine the proteome of the organism for functional and phylogenetic relationships. Finally, the gorgonian EuniceafiShow less
Date Issued
2007
PURL
http://purl.flvc.org/fau/fd/FA00000862
Subject Headings
Marine biology, Pharmaceutical biotechnology, Proteins--Analysis, Gene expression--Research--Methodology, Biomolecules--Analysis
Format
Document (PDF)
Exploration of Methods to Identify Biosynthetic Genes and the Origin of Biosynthesis in Marine Octocorals
Title
Exploration of Methods to Identify Biosynthetic Genes and the Origin of Biosynthesis in Marine Octocorals.
Creator
Ranzer, Llanie Karen, Florida Atlantic University, Kerr, Russell G., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description
The overall goal of this research was to isolate key genes involved in the diterpene biosynthesis from Euniceafusca and Erythropodium caribaeorum using molecular biology techniques. The initial goal was to use fuscol induced cell cultures of Symbiodinium sp. isolated from E. fusca and to develop an approach based on differential display of mRNA-reverse transcription-PeR. Together with inverse PCR, these techniques ultimately provided a full-length farnesyl diphosphate synthase sequence....
Show moreThe overall goal of this research was to isolate key genes involved in the diterpene biosynthesis from Euniceafusca and Erythropodium caribaeorum using molecular biology techniques. The initial goal was to use fuscol induced cell cultures of Symbiodinium sp. isolated from E. fusca and to develop an approach based on differential display of mRNA-reverse transcription-PeR. Together with inverse PCR, these techniques ultimately provided a full-length farnesyl diphosphate synthase sequence. Functional expression of this enzyme was demonstrated with the addition of appropriate substrates and confirmed by chromatography. From this data, degenerate primer based PCR was used to isolate putative geranylgeranyl diphosphate biosynthetic genes from E. caribaeorum. Both chemical and genetic examinations of Pseudopterogorgia elisabethae eggs and their associated Symbiodinium sp. were employed to identify the biosynthetic origin of their diterpenes. Terpene content and biosynthetic capabilities of azooxanthellae eggs demonstrated the presence of pseudopterosins but also indicated that the eggs were not capable of producing these compounds. Likewise, no correlation could be observed for the phylogenetic relationships inferred for the Symbiodinium sp., with that of the terpene chemistry present in P. elisabethae. This finding leads us to speculate about an additional source of terpene production within this coral. Based on these and other recent findings suggesting symbiotic bacteria as the source of secondary metabolites from marine invertebrates, bacterial assemblages from E. caribaeorum were examined. This study revealed considerable phylogenetic bacterial diversity within this coral and the identification of several bacteria known to produce terpenes in other organisms.
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Date Issued
2006
PURL
http://purl.flvc.org/fau/fd/FA00000874
Subject Headings
Coral reef ecology, Diterpenes, Biosynthesis, Terpenes--Synthesis
Format
Document (PDF)
Isolation of the fatty acid synthetase from the marine invertebrate Bugula neritina
Title
Isolation of the fatty acid synthetase from the marine invertebrate Bugula neritina.
Creator
Koh, Francis H., Florida Atlantic University, Kerr, Russell G., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description
The fatty acid synthetase (FAS) from the marine invertebrate Bugula neritina was isolated using cold ethanol precipitation followed by the sequence of G-100 and G-200 size exclusion columns. Native gel analysis indicates the isolation of the FAS and the elution volume from the G-100 column suggests the FAS to be ~282kd. One band with a molecular weight of 66 kDa appeared on the SDS gel of the G-200 sample (F17-30) that eluted at 52.5 mL. The G-200 sample that eluted at 19.2 mL (F1-6)...
Show moreThe fatty acid synthetase (FAS) from the marine invertebrate Bugula neritina was isolated using cold ethanol precipitation followed by the sequence of G-100 and G-200 size exclusion columns. Native gel analysis indicates the isolation of the FAS and the elution volume from the G-100 column suggests the FAS to be ~282kd. One band with a molecular weight of 66 kDa appeared on the SDS gel of the G-200 sample (F17-30) that eluted at 52.5 mL. The G-200 sample that eluted at 19.2 mL (F1-6) displayed two predominant bands on the SDS gel corresponding to molecular weights 66 kDa and 97 kDa. Both F1-6 and F17-30 showed FAS activity displaying de novo production of myristic and palmitic acids. From the sequence of purification starting from the cell-free extract (CFE) to the F17-30 sample, a 240 fold increase in specific activity was observed. The Type II FAS experiments showed no substantial evidence of activity, namely of the beta-Hydroxybutyryl acyl-dehydrase and the enoyl reductase enzymes.
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Date Issued
1998
PURL
http://purl.flvc.org/fcla/dt/15546
Subject Headings
Fatty acids--Synthesis, Marine pharmacology, Bryozoa
Format
Document (PDF)
Isolation, Analysis and Origin of Bioactive Diterpenes in Pseudopterogorgia acerosa.
Title
Isolation, Analysis and Origin of Bioactive Diterpenes in Pseudopterogorgia acerosa.
Creator
Kate, Abhijeet S., Florida Atlantic University, Kerr, Russell G., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description
Nature has served human kind m many ways, one of which is a source of medicines. Natural products from marine sources represent a relatively new area of research and have shown tremendous potential as a source of new chemical entities in drug discovery. Caribbean gorgomans corals of the genus Pseudopterogorgia have been shown to produce a variety of chemically interesting and biologically significant secondary metabolites. ln this dissertation, the Caribbean coral Pseudopterogorgia acerosa...
Show moreNature has served human kind m many ways, one of which is a source of medicines. Natural products from marine sources represent a relatively new area of research and have shown tremendous potential as a source of new chemical entities in drug discovery. Caribbean gorgomans corals of the genus Pseudopterogorgia have been shown to produce a variety of chemically interesting and biologically significant secondary metabolites. ln this dissertation, the Caribbean coral Pseudopterogorgia acerosa has been investigated for the presence of novel diterpenes and these compounds were found to belong to three different classes: pseudopteranoids, bis-pseudopteranoids and lipidyl pseudopteranes. Nine of these were new compounds. The structural elucidation of these compounds was performed using spectroscopic means such as l D and 20 NMR, and mass spectroscopy. There is growing evidence that secondary metabolites isolated from manne invertebrates may actually be produced by a bacterial symbiont. The research studies in our laboratory regarding the source of diterpenes in the selected gorgonian corals suggested a bacterial origin. The hypothesis that coral associated bacteria are the source of diterpenes in the coral P. acerosa, was evaluated using the series of experiments and evidence supported this biosynthetic origin. A study comparing the "gall" tissue and healthy coral tissue in terms of diterpene content and culturable bacterial communities showed that different groups of diterpenes were concentrated in different coral tissue types. It was also observed that the bacterial populations associated with the "gall" and healthy tissues were considerably different. Furthermore, observed specificity in antimicrobial activity of certain groups of compounds against bacteria isolated from the same coral suggested the ecological role of these compounds. This work with "gall" tissue supports the hypothesis that diseased coral tissue represents an excellent source of bioactive natural products for drug discovery. Additionaly, a simple LC-MS method was developed for the analysis of anticancer drug carmustine in plasma.
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Date Issued
2008
PURL
http://purl.flvc.org/fau/fd/FA00000864
Subject Headings
Marine pharmacology, Coral reef ecology--Caribbean Area, Natural products--Synthesis
Format
Document (PDF)
Isolation, Characterization and Synthesis of New Diterpenes from Pseudopterogorgia elisabethae
Title
Isolation, Characterization and Synthesis of New Diterpenes from Pseudopterogorgia elisabethae.
Creator
Wan, Zhongliang, Florida Atlantic University, Kerr, Russell G., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description
Pseudopterogorgia elisabethae is a known source of structurally interesting bioactive metabolites. A detailed search for new, related compounds was undertaken in this study which resulted in the isolation and characterization of more than ten new diterpenes with serrulatane and ileabethane skeletons. Some of the new compounds isolated are closely related terpenes with significant biological activity and others are likely to be key biosynthetic intermediates. As a component of the development...
Show morePseudopterogorgia elisabethae is a known source of structurally interesting bioactive metabolites. A detailed search for new, related compounds was undertaken in this study which resulted in the isolation and characterization of more than ten new diterpenes with serrulatane and ileabethane skeletons. Some of the new compounds isolated are closely related terpenes with significant biological activity and others are likely to be key biosynthetic intermediates. As a component of the development of a production method of anti-inflammatory compounds such as seco-pseudopterosin and elisabethadione, a synthesis of a seco-pseudoperosin aglycone from elisabethatriene was developed.
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Date Issued
2006
PURL
http://purl.flvc.org/fau/fd/FA00000883
Subject Headings
Biosynthesis, Diterpenes--Synthesis, Marine invertebrates, Anti-inflammatory agents
Format
Document (PDF)
Synthesis and testing the intermediacy of diketopiperazines in the biosynthesis of ecteinascidins
Title
Synthesis and testing the intermediacy of diketopiperazines in the biosynthesis of ecteinascidins.
Creator
Jeedigunta, Shanti, Florida Atlantic University, Kerr, Russell G., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description
Ecteinascidin 743 is a trace secondary metabolite isolated from the marine tunicate, Ecteinascidia turbinata. Ecteinacidin 743 a most potent antitumor agent, is currently in Phase II clinical trials in Europe and in the USA. A cell-free extract of Ecteinascidia turbinata was used to investigate the biogenetic origin of the ecteinascidins. Incubation experiments with radiolabeled diketopiperazines indicated that the diketopiperazine of tyrosine is the first committed intermediate in the...
Show moreEcteinascidin 743 is a trace secondary metabolite isolated from the marine tunicate, Ecteinascidia turbinata. Ecteinacidin 743 a most potent antitumor agent, is currently in Phase II clinical trials in Europe and in the USA. A cell-free extract of Ecteinascidia turbinata was used to investigate the biogenetic origin of the ecteinascidins. Incubation experiments with radiolabeled diketopiperazines indicated that the diketopiperazine of tyrosine is the first committed intermediate in the biosynthesis of ecteinascidins. Phenylalanine diketopiperazine was not transformed into the ecteinascidins indicating that this cyclic dipeptide is not an intermediate in the biosynthesis of ecteinascidins. The diketopiperazine of DOPA was used as a cold carrier demonstrating that the diketopiperazine of tyrosine is oxidized to DOPA diketopiperazine and then further transformed to the ecteinascidins.
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Date Issued
2000
PURL
http://purl.flvc.org/fcla/dt/15754
Subject Headings
Sea squirts, Dopa, Tunicata
Format
Document (PDF)