The Experts below are selected from a list of 63 Experts worldwide ranked by ideXlab platform
William H Gerwick - One of the best experts on this subject based on the ideXlab platform.
-
expanding the described metabolome of the marine cyanobacterium moorea producens jhb through orthogonal natural products workflows
PLOS ONE, 2015Co-Authors: Paul D Boudreau, Emily A Monroe, Suneet Mehrotra, Shane Desfor, Anton Korobeynikov, David H Sherman, Thomas F Murray, Lena Gerwick, Pieter C Dorrestein, William H GerwickAbstract:Moorea producens JHB, a Jamaican strain of tropical filamentous marine cyanobacteria, has been extensively studied by traditional natural products techniques. These previous bioassay and structure guided isolations led to the discovery of two exciting classes of natural products, Hectochlorin (1) and jamaicamides A (2) and B (3). In the current study, mass spectrometry-based ‘molecular networking’ was used to visualize the metabolome of Moorea producens JHB, and both guided and enhanced the isolation workflow, revealing additional metabolites in these compound classes. Further, we developed additional insight into the metabolic capabilities of this strain by genome sequencing analysis, which subsequently led to the isolation of a compound unrelated to the jamaicamide and Hectochlorin families. Another approach involved stimulation of the biosynthesis of a minor jamaicamide metabolite by cultivation in modified media, and provided insights about the underlying biosynthetic machinery as well as preliminary structure-activity information within this structure class. This study demonstrated that these orthogonal approaches are complementary and enrich secondary metabolomic coverage even in an extensively studied bacterial strain.
-
PB Marine Cyanobacteria 175Ramaswamy et al. 5 The Secondary Metabolites and Biosynthetic Gene Clusters of Marine Cyanobacteria. Applications in
2015Co-Authors: Aishwarya V Ramaswamy, Patricia M. Flatt, J. Edwards, Luke T. Simmons, Bingnan Han, William H GerwickAbstract:Marine cyanobacteria have proven to be one of the most versatile marine producers of secondary metabolites. Many of these metabolites demonstrate antiproliferative activity (e.g. curacin A, dolastatins), acute cytotoxic activity (e.g. apratoxin, Hectochlorin) or have specific neurotoxic activity (e.g. kalkitoxin, antillatoxin), making them invaluable as potential therapeutic leads or pharmacological tools. The predominant biogenetic theme in cyanobacterial natural products chemistry is the integration of polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS) along with a variety of unusual tailoring or modifying enzymes, and accounts for the tremendous structural diversity of their metabolites. Only recently has the genetic architecture of several cyanobacterial biosynthetic gene clusters been determined, and studies to understand and exploit this biosynthentic machinery present an exciting new frontier. This chapter will summarize the properties of several notable metabolites from marine cyanobacteria that have clinical or pharmacological applications followed by a detailed account of their biosyntheses at the molecular genetic level and their potential applications in biotechnology. 1
-
Analogs of Hectochlorin Deduced from the Molecular Network.
2015Co-Authors: Paul D Boudreau, Emily A Monroe, Suneet Mehrotra, Shane Desfor, Anton Korobeynikov, David H Sherman, Thomas F Murray, Lena Gerwick, Pieter C Dorrestein, William H GerwickAbstract:Analogs of Hectochlorin Deduced from the Molecular Network.
-
Hectochlorin (1) isotope pattern within the M. producens JHB network.
2015Co-Authors: Paul D Boudreau, Emily A Monroe, Suneet Mehrotra, Shane Desfor, Anton Korobeynikov, David H Sherman, Thomas F Murray, Lena Gerwick, Pieter C Dorrestein, William H GerwickAbstract:The presence of 35Cl or 37Cl within specific Hectochlorin molecules yielded different parent masses and fragment spectra. The species with both 35Cl atoms has an m/z of 665, the species with one 35Cl and one 37Cl atom has and m/z of 667, and the species with 37Cl atoms has an m/z of 669. Because of this the fragment spectra share only masses from those fragments without chlorine atoms, and those fragments bearing the chlorine atoms show the same mass differences as their parent masses.
-
cloning and biochemical characterization of the Hectochlorin biosynthetic gene cluster from the marine cyanobacterium lyngbya majuscula
Journal of Natural Products, 2007Co-Authors: Aishwarya V Ramaswamy, Carla M Sorrels, William H GerwickAbstract:Cyanobacteria, or blue-green algae, are a rich source of novel bioactive secondary metabolites that have potential applications as antimicrobial or anticancer agents or useful probes in cell biology studies. A Jamaican collection of the cyanobacterium Lyngbya majuscula has yielded several unique compounds including Hectochlorin ( 1) and the jamaicamides A-C ( 5- 7). Hectochlorin has remarkable antifungal and cytotoxic properties. In this study, we have isolated the Hectochlorin biosynthetic gene cluster ( hct) from L. majuscula to obtain details regarding its biosynthesis at the molecular genetic level. The genetic architecture and domain organization appear to be colinear with respect to its biosynthesis and consists of eight open reading frames (ORFs) spanning 38 kb. An unusual feature of the cluster is the presence of ketoreductase (KR) domains in two peptide synthetase modules, which are predicted to be involved in the formation of the two 2,3-dihydroxyisovaleric acid (DHIV) units. This biosynthetic motif has only recently been described in cereulide, valinomycin, and cryptophycin biosynthesis, and hence, this is only the second such report of an embedded ketoreductase in a cyanobacterial secondary metabolite gene cluster. Also present at the downstream end of the cluster are two cytochrome P450 monooxygenases, which are likely involved in the formation of the DHIV units. A putative halogenase, at the beginning of the gene cluster, is predicted to form 5,5-dichlorohexanoic acid.
Kerry L Mcphail - One of the best experts on this subject based on the ideXlab platform.
-
apratoxin h and apratoxin a sulfoxide from the red sea cyanobacterium moorea producens
Journal of Natural Products, 2013Co-Authors: Christopher C. Thornburg, Diaa T A Youssef, Lamiaa A Shaala, Elise S Cowley, Justyna Sikorska, Jane E Ishmael, Kerry L McphailAbstract:Cultivation of the marine cyanobacterium Moorea producens, collected from the Nabq Mangroves in the Gulf of Aqaba (Red Sea), led to the isolation of new apratoxin analogues apratoxin H (1) and apratoxin A sulfoxide (2), together with the known apratoxins A–C, lyngbyabellin B, and Hectochlorin. The absolute configuration of these new potent cytotoxins was determined by chemical degradation, MS, NMR, and CD spectroscopy. Apratoxin H (1) contains pipecolic acid in place of the proline residue present in apratoxin A, expanding the known suite of naturally occurring analogues that display amino acid substitutions within the final module of the apratoxin biosynthetic pathway. The oxidation site of apratoxin A sulfoxide (2) was deduced from MS fragmentation patterns and IR data, and 2 could not be generated experimentally by oxidation of apratoxin A. The cytotoxicity of 1 and 2 to human NCI-H460 lung cancer cells (IC50 = 3.4 and 89.9 nM, respectively) provides further insight into the structure–activity relation...
-
Apratoxin H and Apratoxin A Sulfoxide from the Red Sea Cyanobacterium Moorea producens
2013Co-Authors: Christopher C. Thornburg, Diaa T A Youssef, Lamiaa A Shaala, Elise S Cowley, Justyna Sikorska, Jane E Ishmael, Kerry L McphailAbstract:Cultivation of the marine cyanobacterium Moorea producens, collected from the Nabq Mangroves in the Gulf of Aqaba (Red Sea), led to the isolation of new apratoxin analogues apratoxin H (1) and apratoxin A sulfoxide (2), together with the known apratoxins A–C, lyngbyabellin B, and Hectochlorin. The absolute configuration of these new potent cytotoxins was determined by chemical degradation, MS, NMR, and CD spectroscopy. Apratoxin H (1) contains pipecolic acid in place of the proline residue present in apratoxin A, expanding the known suite of naturally occurring analogues that display amino acid substitutions within the final module of the apratoxin biosynthetic pathway. The oxidation site of apratoxin A sulfoxide (2) was deduced from MS fragmentation patterns and IR data, and 2 could not be generated experimentally by oxidation of apratoxin A. The cytotoxicity of 1 and 2 to human NCI-H460 lung cancer cells (IC50 = 3.4 and 89.9 nM, respectively) provides further insight into the structure–activity relationships in the apratoxin series. Phylogenetic analysis of the apratoxin-producing cyanobacterial strains belonging to the genus Moorea, coupled with the recently annotated apratoxin biosynthetic pathway, supports the notion that apratoxin production and structural diversity may be specific to their geographical niche
Christopher C. Thornburg - One of the best experts on this subject based on the ideXlab platform.
-
apratoxin h and apratoxin a sulfoxide from the red sea cyanobacterium moorea producens
Journal of Natural Products, 2013Co-Authors: Christopher C. Thornburg, Diaa T A Youssef, Lamiaa A Shaala, Elise S Cowley, Justyna Sikorska, Jane E Ishmael, Kerry L McphailAbstract:Cultivation of the marine cyanobacterium Moorea producens, collected from the Nabq Mangroves in the Gulf of Aqaba (Red Sea), led to the isolation of new apratoxin analogues apratoxin H (1) and apratoxin A sulfoxide (2), together with the known apratoxins A–C, lyngbyabellin B, and Hectochlorin. The absolute configuration of these new potent cytotoxins was determined by chemical degradation, MS, NMR, and CD spectroscopy. Apratoxin H (1) contains pipecolic acid in place of the proline residue present in apratoxin A, expanding the known suite of naturally occurring analogues that display amino acid substitutions within the final module of the apratoxin biosynthetic pathway. The oxidation site of apratoxin A sulfoxide (2) was deduced from MS fragmentation patterns and IR data, and 2 could not be generated experimentally by oxidation of apratoxin A. The cytotoxicity of 1 and 2 to human NCI-H460 lung cancer cells (IC50 = 3.4 and 89.9 nM, respectively) provides further insight into the structure–activity relation...
Lik Tong Tan - One of the best experts on this subject based on the ideXlab platform.
-
Filamentous tropical marine cyanobacteria: a rich source of natural products for anticancer drug discovery
Journal of Applied Phycology, 2010Co-Authors: Lik Tong TanAbstract:A plethora of structurally novel bioactive secondary metabolites have been reported from the prokaryotic filamentous marine cyanobacteria in the past few decades. In addition to the production of harmful toxins, these marine blue-green algae are emerging as an important source of anticancer drugs. The majority of these potent biomolecules, including the dolastatins, curacin A, Hectochlorin, the apratoxins, and the lyngbyabellins, belongs to the mixed polyketide–polypeptide structural class. Furthermore, a high proportion of these natural products target eukaryotic cytoskeleton, such as tubulin and actin microfilaments, making them an attractive source of potential anticancer drugs. In recent years, a number of potent marine cyanobacteria have also been reported to modulate cell death and apoptosis in cancer cells as well as target enzymes such as histone deacetylase. A number of marine cyanobacterial compounds have also served as structural templates for the generation of new drug leads, further attesting to the importance of these marine microbes as an important source of new pharmaceuticals. This review serves to highlight the chemistry and biology of selected anticancer marine cyanobacterial natural products exhibiting significant biological activities in the nanomolar or submicromolar range, and their discussion will be based on the different modes of action.
-
bioactive natural products from marine cyanobacteria for drug discovery
Phytochemistry, 2007Co-Authors: Lik Tong TanAbstract:The prokaryotic marine cyanobacteria continue to be an important source of structurally bioactive secondary metabolites. A majority of these molecules are nitrogen-containing compounds biosynthesized by large multimodular nonribosomal polypeptide (NRP) or mixed polyketide-NRP enzymatic systems. A total of 128 marine cyanobacterial alkaloids, published in the literature between January 2001 and December 2006, are presented in this review with emphasis on their biosynthesis and biological activities. In addition, a number of highly cytotoxic compounds such as Hectochlorin, lyngbyabellins, apratoxins, and aurilides have been identified as potential lead compounds for the development of anticancer agents. A brief coverage on the distribution of natural product biosynthetic genes as well as the mechanisms of tailoring enzymes involved in the biosynthesis of cyanobacterial compounds will also be given.
Justyna Sikorska - One of the best experts on this subject based on the ideXlab platform.
-
apratoxin h and apratoxin a sulfoxide from the red sea cyanobacterium moorea producens
Journal of Natural Products, 2013Co-Authors: Christopher C. Thornburg, Diaa T A Youssef, Lamiaa A Shaala, Elise S Cowley, Justyna Sikorska, Jane E Ishmael, Kerry L McphailAbstract:Cultivation of the marine cyanobacterium Moorea producens, collected from the Nabq Mangroves in the Gulf of Aqaba (Red Sea), led to the isolation of new apratoxin analogues apratoxin H (1) and apratoxin A sulfoxide (2), together with the known apratoxins A–C, lyngbyabellin B, and Hectochlorin. The absolute configuration of these new potent cytotoxins was determined by chemical degradation, MS, NMR, and CD spectroscopy. Apratoxin H (1) contains pipecolic acid in place of the proline residue present in apratoxin A, expanding the known suite of naturally occurring analogues that display amino acid substitutions within the final module of the apratoxin biosynthetic pathway. The oxidation site of apratoxin A sulfoxide (2) was deduced from MS fragmentation patterns and IR data, and 2 could not be generated experimentally by oxidation of apratoxin A. The cytotoxicity of 1 and 2 to human NCI-H460 lung cancer cells (IC50 = 3.4 and 89.9 nM, respectively) provides further insight into the structure–activity relation...
-
Apratoxin H and Apratoxin A Sulfoxide from the Red Sea Cyanobacterium Moorea producens
2013Co-Authors: Christopher C. Thornburg, Diaa T A Youssef, Lamiaa A Shaala, Elise S Cowley, Justyna Sikorska, Jane E Ishmael, Kerry L McphailAbstract:Cultivation of the marine cyanobacterium Moorea producens, collected from the Nabq Mangroves in the Gulf of Aqaba (Red Sea), led to the isolation of new apratoxin analogues apratoxin H (1) and apratoxin A sulfoxide (2), together with the known apratoxins A–C, lyngbyabellin B, and Hectochlorin. The absolute configuration of these new potent cytotoxins was determined by chemical degradation, MS, NMR, and CD spectroscopy. Apratoxin H (1) contains pipecolic acid in place of the proline residue present in apratoxin A, expanding the known suite of naturally occurring analogues that display amino acid substitutions within the final module of the apratoxin biosynthetic pathway. The oxidation site of apratoxin A sulfoxide (2) was deduced from MS fragmentation patterns and IR data, and 2 could not be generated experimentally by oxidation of apratoxin A. The cytotoxicity of 1 and 2 to human NCI-H460 lung cancer cells (IC50 = 3.4 and 89.9 nM, respectively) provides further insight into the structure–activity relationships in the apratoxin series. Phylogenetic analysis of the apratoxin-producing cyanobacterial strains belonging to the genus Moorea, coupled with the recently annotated apratoxin biosynthetic pathway, supports the notion that apratoxin production and structural diversity may be specific to their geographical niche