A cytotoxic pentadecapeptide from a South African Didemnid tunicate
- Gallegos, D, Serrill, J, Parker-Nance, Shirley, Dorrington, Rosemary A, Ishmael, J, McPhail, Kerry L
- Authors: Gallegos, D , Serrill, J , Parker-Nance, Shirley , Dorrington, Rosemary A , Ishmael, J , McPhail, Kerry L
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/65935 , vital:28863 , https://doi.org/10.1055/s-0036-1596683
- Description: publisher version , The rate of discovery of new natural product chemical entities has plateaued, and unique populations of endemic, biologically diverse sessile marine organisms represent increasingly critical opportunities to discover new chemistry. Discovery of the mandelalides [1] as potent inhibitors of cancer cell growth from the new South African tunicate Lissoclinum mandelai is an example of the diverse suites of metabolites with potent biological activities that have been isolated from tunicates and other filter-feeding sessile marine organisms that house complex microbial consortia. Further investigation of archived and new tunicate collections from Algoa Bay, South Africa, has revealed a group of didemnid tunicates with an unusual gelatinous morphology similar to Lissoclinum mandelai. Using a bioassay-guided isolation approach, a new “gelatinous” species of the genus Didemnum has yielded a cytotoxic pentadecapeptide with a molecular mass of 1603.7688 Da, comprising fifteen residues including both proteinogenic and non-proteinogenic amino acids. The pure compound inhibited both HeLa cervical cancer and NCI-H460 non-small cell lung cancer cell lines when tested at 30 nM in preliminary assays against cells seeded at low densities. Inhibition of cancer cells at low starting density may be indicative of an anti-proliferative mechanism of action. The compound did not show antibacterial activity against Vibrio cholera. Didemnin B and its clinically approved analogue dehydrodidemnin B (plitidepsin, Aplidin®) [2, 3] are important macrocyclic depsipeptides from a didemnid tunicate. The pentadecapeptide reported here provides justification for our continued investigation of unique, endemic didemnid tunicates from South Africa as a source of new macrocyclic natural products with cytotoxic, anti-viral or antimicrobial activity. , We acknowledge the South African government for permission to collect the subject tunicate (Collection Permit No. 278 RES2013/43)
- Full Text: false
- Authors: Gallegos, D , Serrill, J , Parker-Nance, Shirley , Dorrington, Rosemary A , Ishmael, J , McPhail, Kerry L
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/65935 , vital:28863 , https://doi.org/10.1055/s-0036-1596683
- Description: publisher version , The rate of discovery of new natural product chemical entities has plateaued, and unique populations of endemic, biologically diverse sessile marine organisms represent increasingly critical opportunities to discover new chemistry. Discovery of the mandelalides [1] as potent inhibitors of cancer cell growth from the new South African tunicate Lissoclinum mandelai is an example of the diverse suites of metabolites with potent biological activities that have been isolated from tunicates and other filter-feeding sessile marine organisms that house complex microbial consortia. Further investigation of archived and new tunicate collections from Algoa Bay, South Africa, has revealed a group of didemnid tunicates with an unusual gelatinous morphology similar to Lissoclinum mandelai. Using a bioassay-guided isolation approach, a new “gelatinous” species of the genus Didemnum has yielded a cytotoxic pentadecapeptide with a molecular mass of 1603.7688 Da, comprising fifteen residues including both proteinogenic and non-proteinogenic amino acids. The pure compound inhibited both HeLa cervical cancer and NCI-H460 non-small cell lung cancer cell lines when tested at 30 nM in preliminary assays against cells seeded at low densities. Inhibition of cancer cells at low starting density may be indicative of an anti-proliferative mechanism of action. The compound did not show antibacterial activity against Vibrio cholera. Didemnin B and its clinically approved analogue dehydrodidemnin B (plitidepsin, Aplidin®) [2, 3] are important macrocyclic depsipeptides from a didemnid tunicate. The pentadecapeptide reported here provides justification for our continued investigation of unique, endemic didemnid tunicates from South Africa as a source of new macrocyclic natural products with cytotoxic, anti-viral or antimicrobial activity. , We acknowledge the South African government for permission to collect the subject tunicate (Collection Permit No. 278 RES2013/43)
- Full Text: false
Cytotoxic activity of marine sponge extracts from the sub-Antarctic Islands and the Southern Ocean
- Olsen, Elisabeth, De Cerf, Christopher, Dziwornu, Godwin A, Puccinelli, Eleonora, Parker-Nance, Shirley, Ansorge, Isabelle J, Samaai, Toufiek, Dingle, Laura M K, Edkins, Adrienne L, Sunassee, Suthananda N
- Authors: Olsen, Elisabeth , De Cerf, Christopher , Dziwornu, Godwin A , Puccinelli, Eleonora , Parker-Nance, Shirley , Ansorge, Isabelle J , Samaai, Toufiek , Dingle, Laura M K , Edkins, Adrienne L , Sunassee, Suthananda N
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66300 , vital:28931 , https://doi.org/10.17159/sajs.2016/20160202
- Description: publisher version , Over the past 50 years, marine invertebrates, especially sponges, have proven to be a valuable source of new and/or bioactive natural products that have the potential to be further developed as lead compounds for pharmaceutical applications. Although marine benthic invertebrate communities occurring off the coast of South Africa have been explored for their biomedicinal potential, the natural product investigation of marine sponges from the sub-Antarctic Islands in the Southern Ocean for the presence of bioactive secondary metabolites has been relatively unexplored thus far. We report here the results for the biological screening of both aqueous and organic extracts prepared from nine specimens of eight species of marine sponges, collected from around Marion Island and the Prince Edward Islands in the Southern Ocean, for their cytotoxic activity against three cancer cell lines. The results obtained through this multidisciplinary collaborative research effort by exclusively South African institutions has provided an exciting opportunity to discover cytotoxic compounds from sub-Antarctic sponges, whilst contributing to our understanding of the biodiversity and geographic distributions of these cold-water invertebrates. Therefore, we acknowledge here the various contributions of the diverse scientific disciplines that played a pivotal role in providing the necessary platform for the future natural products chemistry investigation of these marine sponges from the sub- Antarctic Islands and the Southern Ocean. Significance: This study will contribute to understanding the biodiversity and geographic distributions of sponges in the Southern Ocean. This multidisciplinary project has enabled the investigation of marine sponges for the presence of cytotoxic compounds. Further investigation will lead to the isolation and identification of cytotoxic compounds present in the active sponge extracts. , University of Cape Town; South African Medical Research Council; National Research Foundation (South Africa); CANSA; Rhodes University; Department of Science and Technology; Department of Environmental Affairs; SANAP
- Full Text:
- Authors: Olsen, Elisabeth , De Cerf, Christopher , Dziwornu, Godwin A , Puccinelli, Eleonora , Parker-Nance, Shirley , Ansorge, Isabelle J , Samaai, Toufiek , Dingle, Laura M K , Edkins, Adrienne L , Sunassee, Suthananda N
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/66300 , vital:28931 , https://doi.org/10.17159/sajs.2016/20160202
- Description: publisher version , Over the past 50 years, marine invertebrates, especially sponges, have proven to be a valuable source of new and/or bioactive natural products that have the potential to be further developed as lead compounds for pharmaceutical applications. Although marine benthic invertebrate communities occurring off the coast of South Africa have been explored for their biomedicinal potential, the natural product investigation of marine sponges from the sub-Antarctic Islands in the Southern Ocean for the presence of bioactive secondary metabolites has been relatively unexplored thus far. We report here the results for the biological screening of both aqueous and organic extracts prepared from nine specimens of eight species of marine sponges, collected from around Marion Island and the Prince Edward Islands in the Southern Ocean, for their cytotoxic activity against three cancer cell lines. The results obtained through this multidisciplinary collaborative research effort by exclusively South African institutions has provided an exciting opportunity to discover cytotoxic compounds from sub-Antarctic sponges, whilst contributing to our understanding of the biodiversity and geographic distributions of these cold-water invertebrates. Therefore, we acknowledge here the various contributions of the diverse scientific disciplines that played a pivotal role in providing the necessary platform for the future natural products chemistry investigation of these marine sponges from the sub- Antarctic Islands and the Southern Ocean. Significance: This study will contribute to understanding the biodiversity and geographic distributions of sponges in the Southern Ocean. This multidisciplinary project has enabled the investigation of marine sponges for the presence of cytotoxic compounds. Further investigation will lead to the isolation and identification of cytotoxic compounds present in the active sponge extracts. , University of Cape Town; South African Medical Research Council; National Research Foundation (South Africa); CANSA; Rhodes University; Department of Science and Technology; Department of Environmental Affairs; SANAP
- Full Text:
Keeping it in the family: coevolution of latrunculid sponges and their dominant bacterial symbionts
- Matcher, Gwynneth F, Waterworth, Samantha C, Walmsley, Tara A, Matsatsa, Tendayi, Parker-Nance, Shirley, Davies-Coleman, Michael T, Dorrington, Rosemary A
- Authors: Matcher, Gwynneth F , Waterworth, Samantha C , Walmsley, Tara A , Matsatsa, Tendayi , Parker-Nance, Shirley , Davies-Coleman, Michael T , Dorrington, Rosemary A
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/65603 , vital:28818 , https://doi.org/10.1002/mbo3.417
- Description: publisher version , The Latrunculiidae are a family of cold water sponges known for their production of bioactive pyrroloiminoquinone alkaloids. Previously it was shown that the bacterial community associated with a Tsitsikamma sponge species comprises unusual bacterial taxa and is dominated by a novel Betaproteobacterium. Here, we have characterized the bacterial communities associated with six latrunculid species representing three genera (Tsitsikamma, Cyclacanthia, and Latrunculia) as well as a Mycale species, collected from Algoa Bay on the South African southeast coast. The bacterial communities of all seven sponge species were dominated by a single Betaproteobacterium operational taxonomic unit (OTU0.03), while a second OTU0.03 was dominant in the Mycale sp. The Betaproteobacteria OTUs from the different latrunculid sponges are closely related and their phylogenetic relationship follows that of their hosts. We propose that the latrunculid Betaproteobacteria OTUs are members of a specialized group of sponge symbionts that may have coevolved with their hosts. A single dominant Spirochaetae OTU0.03 was present in the Tsitsikamma and Cyclacanthia sponge species, but absent from the Latrunculia and Mycale sponges. This study sheds new light on the interactions between latrunculid sponges and their bacterial communities and may point to the potential involvement of dominant symbionts in the biosynthesis of the bioactive secondary metabolites. , This research was supported by a SARChI grant from the South African National Research Foundation (NRF, GUN: 87583) and the Rhodes University Sandisa Imbewu Programme. S. C. W. was supported by an NRF Innovation PhD Scholarship and a Rhodes University Henderson PhD Scholarship. T. A. W. was supported by PhD Fellowships from the NRF and the German Academic Exchange Service (DAAD)
- Full Text:
- Authors: Matcher, Gwynneth F , Waterworth, Samantha C , Walmsley, Tara A , Matsatsa, Tendayi , Parker-Nance, Shirley , Davies-Coleman, Michael T , Dorrington, Rosemary A
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/65603 , vital:28818 , https://doi.org/10.1002/mbo3.417
- Description: publisher version , The Latrunculiidae are a family of cold water sponges known for their production of bioactive pyrroloiminoquinone alkaloids. Previously it was shown that the bacterial community associated with a Tsitsikamma sponge species comprises unusual bacterial taxa and is dominated by a novel Betaproteobacterium. Here, we have characterized the bacterial communities associated with six latrunculid species representing three genera (Tsitsikamma, Cyclacanthia, and Latrunculia) as well as a Mycale species, collected from Algoa Bay on the South African southeast coast. The bacterial communities of all seven sponge species were dominated by a single Betaproteobacterium operational taxonomic unit (OTU0.03), while a second OTU0.03 was dominant in the Mycale sp. The Betaproteobacteria OTUs from the different latrunculid sponges are closely related and their phylogenetic relationship follows that of their hosts. We propose that the latrunculid Betaproteobacteria OTUs are members of a specialized group of sponge symbionts that may have coevolved with their hosts. A single dominant Spirochaetae OTU0.03 was present in the Tsitsikamma and Cyclacanthia sponge species, but absent from the Latrunculia and Mycale sponges. This study sheds new light on the interactions between latrunculid sponges and their bacterial communities and may point to the potential involvement of dominant symbionts in the biosynthesis of the bioactive secondary metabolites. , This research was supported by a SARChI grant from the South African National Research Foundation (NRF, GUN: 87583) and the Rhodes University Sandisa Imbewu Programme. S. C. W. was supported by an NRF Innovation PhD Scholarship and a Rhodes University Henderson PhD Scholarship. T. A. W. was supported by PhD Fellowships from the NRF and the German Academic Exchange Service (DAAD)
- Full Text:
Latrunculid sponges, their microbial communities and secondary metabolites: connecting conserved bacterial symbionts to pyrroloiminoquinone production
- Dorrington, Rosemary A, Hilliar, Storm Hannah, Kalinski, Jarmo-Charles J, Krause, Rui W M, McPhail, Kerry L, Parker-Nance, Shirley, Wlalmsley, Tara A, Waterworth, Samantha C
- Authors: Dorrington, Rosemary A , Hilliar, Storm Hannah , Kalinski, Jarmo-Charles J , Krause, Rui W M , McPhail, Kerry L , Parker-Nance, Shirley , Wlalmsley, Tara A , Waterworth, Samantha C
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/65915 , vital:28858 , https://doi.org/10.1055/s-0036-1596655
- Description: publisher version , The Latrunculiidae are cold water sponges known for their production of bioactive pyrroloiminoquinone alkaloids (e.g. makaluvamines, discorhabdins and tsitsikammamines). Since pyrroloiminoquinones have also been isolated from sponges belonging to other families, ascidians and microorganisms, the biosynthetic origin of these alkaloids in latrunculid sponges is likely microbial. This study focuses on the secondary metabolites produced by closely-related Tsitsikamma species and Cyclacanthia bellae, all latrunculid sponges endemic to Algoa Bay on the South African southeast coast. The sponges produced suites of related pyrroloiminoquinones, including tsitsikammine A and B, and discohabdin C and V, the combination and relative abundance of which is species-specific. Characterisation of the diversity of sponge-associated bacterial communities revealed the unprecedented conservation of two dominant bacterial species. The first, a Betaproteobacterium, is also found in other latrunculids and related sponge families, representing a novel clade of sponge endosymbionts that have co-evolved with their hosts. The second conserved bacterial symbiont is a spirochaete found only in Cyclacanthia and Tsitsikamma species that is likely to have been recruited from free-living spirochaetes in the environment. This study sheds new light on the interactions between latrunculid sponges, their dominant bacterial symbionts, and the potential involvement of these bacteria in pyrroloiminoquinone biosynthesis.
- Full Text: false
- Authors: Dorrington, Rosemary A , Hilliar, Storm Hannah , Kalinski, Jarmo-Charles J , Krause, Rui W M , McPhail, Kerry L , Parker-Nance, Shirley , Wlalmsley, Tara A , Waterworth, Samantha C
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/65915 , vital:28858 , https://doi.org/10.1055/s-0036-1596655
- Description: publisher version , The Latrunculiidae are cold water sponges known for their production of bioactive pyrroloiminoquinone alkaloids (e.g. makaluvamines, discorhabdins and tsitsikammamines). Since pyrroloiminoquinones have also been isolated from sponges belonging to other families, ascidians and microorganisms, the biosynthetic origin of these alkaloids in latrunculid sponges is likely microbial. This study focuses on the secondary metabolites produced by closely-related Tsitsikamma species and Cyclacanthia bellae, all latrunculid sponges endemic to Algoa Bay on the South African southeast coast. The sponges produced suites of related pyrroloiminoquinones, including tsitsikammine A and B, and discohabdin C and V, the combination and relative abundance of which is species-specific. Characterisation of the diversity of sponge-associated bacterial communities revealed the unprecedented conservation of two dominant bacterial species. The first, a Betaproteobacterium, is also found in other latrunculids and related sponge families, representing a novel clade of sponge endosymbionts that have co-evolved with their hosts. The second conserved bacterial symbiont is a spirochaete found only in Cyclacanthia and Tsitsikamma species that is likely to have been recruited from free-living spirochaetes in the environment. This study sheds new light on the interactions between latrunculid sponges, their dominant bacterial symbionts, and the potential involvement of these bacteria in pyrroloiminoquinone biosynthesis.
- Full Text: false
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