Dataset Information

Dragonamide E, a modified linear lipopeptide from Lyngbya majuscula with antileishmanial activity.

ABSTRACT: Tropical parasitic and infectious diseases, such as leishmaniasis, pose enormous global health threats, but are largely neglected in commercial drug discovery programs. However, the Panama International Cooperative Biodiversity Group (ICBG) has been working to identify novel treatments for malaria, Chagas' disease, and leishmaniasis through an investigation of plants and microorganisms from Panama. We have pursued activity-guided isolation from an extract of Lyngbya majuscula that was found to be active against leishmaniasis. A new modified linear peptide from the dragonamide series was isolated, dragonamide E (1), along with two known modified linear peptides, dragonamide A (2) and herbamide B (3). Dragonamides A and E and herbamide B exhibited antileishmanial activity with IC50 values of 6.5, 5.1, and 5.9 microM, respectively. Spectroscopic and stereochemical data for dragonamide E (1) and herbamide B (3; the spectroscopic and stereochemical data for this substance is incomplete in the literature) are presented as well as comparisons of biological activity within the dragonamide compound family. Biosynthetic differences among marine compounds with a terminal free amide are also discussed.

SUBMITTER: Balunas MJ

PROVIDER: S-EPMC2834186 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dragonamide E, a modified linear lipopeptide from Lyngbya majuscula with antileishmanial activity.

Balunas Marcy J MJ Linington Roger G RG Tidgewell Kevin K Fenner Amanda M AM Ureña Luis-David LD Togna Gina Della GD Kyle Dennis E DE Gerwick William H WH

Journal of natural products 20100101 1

Tropical parasitic and infectious diseases, such as leishmaniasis, pose enormous global health threats, but are largely neglected in commercial drug discovery programs. However, the Panama International Cooperative Biodiversity Group (ICBG) has been working to identify novel treatments for malaria, Chagas' disease, and leishmaniasis through an investigation of plants and microorganisms from Panama. We have pursued activity-guided isolation from an extract of Lyngbya majuscula that was found to b ...[more]

PMID: 20030365

Similar Datasets

Project description:BACKGROUND: Lyngbya majuscula CCAP 1446/4 is a N2-fixing filamentous nonheterocystous strain that contains two NiFe-hydrogenases: an uptake (encoded by hupSL) and a bidirectional enzyme (encoded by hoxEFUYH). The biosynthesis/maturation of NiFe-hydrogenases is a complex process requiring several accessory proteins for e.g. for the incorporation of metals and ligands in the active center (large subunit), and the insertion of the FeS clusters (small subunit). The last step in the maturation of the large subunit is the cleavage of a C-terminal peptide from its precursor by a specific endopeptidase. Subsequently, the mature large and small subunits can assemble forming a functional enzyme. RESULTS: In this work we demonstrated that, in L. majuscula, the structural genes encoding the bidirectional hydrogenase are cotranscribed, and that hoxW (the gene encoding its putative specific endopeptidase) is in the same chromosomal region but transcribed from a different promoter. The gene encoding the putative specific uptake hydrogenase endopeptidase, hupW, can be cotranscribed with the structural genes but it has its own promoter. hoxH, hupL, hoxW and hupW transcription was followed in L. majuscula cells grown under N2-fixing and non-N2-fixing conditions over a 12 h light/12 h dark cycle. The transcription of hoxH, hoxW and hupW did not vary remarkably in the conditions tested, while the hupL transcript levels are significantly higher under N2-fixing conditions with a peak occurring in the transition between the light and the dark phase. Furthermore, the putative endopeptidases transcript levels, in particular hoxW, are lower than those of the respective hydrogenase structural genes. CONCLUSION: The data presented here indicate that in L. majuscula the genes encoding the putative hydrogenases specific endopeptidases, hoxW and hupW, are transcribed from their own promoters. Their transcript levels do not vary notably in the conditions tested, suggesting that HoxW and HupW are probably constantly present and available in the cells. These results, together with the fact that the putative endopeptidases transcript levels, in particular for hoxW, are lower than those of the structural genes, imply that the activity of the hydrogenases is mainly correlated to the transcription levels of the structural genes. The analysis of the promoter regions indicates that hupL and hupW might be under the control of different transcription factor(s), while both hoxH and xisH (hoxW) promoters could be under the control of LexA.

Dataset Information

Dragonamide E, a modified linear lipopeptide from Lyngbya majuscula with antileishmanial activity.

Publications

Dragonamide E, a modified linear lipopeptide from Lyngbya majuscula with antileishmanial activity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets