TY  - JOUR
A1  - Abdelmohsen, Usama Ramadan
A1  - Cheng, Cheng
A1  - Viegelmann, Christina
A1  - Zhang, Tong
A1  - Grkovic, Tanja
A1  - Ahmed, Safwat
A1  - Quinn, Ronald J.
A1  - Hentschel, Ute
A1  - Edrada-Ebel, RuAngelie
T1  - Dereplication Strategies for Targeted Isolation of New Antitrypanosomal Actinosporins A and B from a Marine Sponge Associated-Actinokineospora sp EG49
JF  - Marine Drugs
N2  - High resolution Fourier transform mass spectrometry (HRFTMS) and nuclear magnetic resonance (NMR) spectroscopy were employed as complementary metabolomic tools to dereplicate the chemical profile of the new and antitrypanosomally active sponge-associated bacterium Actinokineospora sp. EG49 extract. Principal Component (PCA), hierarchical clustering (HCA), and orthogonal partial least square-discriminant analysis (OPLS-DA) were used to evaluate the HRFTMS and NMR data of crude extracts from four different fermentation approaches. Statistical analysis identified the best culture one-strain-many-compounds (OSMAC) condition and extraction procedure, which was used for the isolation of novel bioactive metabolites. As a result, two new O-glycosylated angucyclines, named actinosporins A (1) and B (2), were isolated from the broth culture of Actinokineospora sp. strain EG49, which was cultivated from the Red Sea sponge Spheciospongia vagabunda. The structures of actinosporins A and B were determined by 1D- and 2D-NMR techniques, as well as high resolution tandem mass spectrometry. Testing for antiparasitic properties showed that actinosporin A exhibited activity against Trypanosoma brucei brucei with an IC₅₀ value of 15 µM; however no activity was detected against Leishmania major and Plasmodium falciparum, therefore suggesting its selectivity against the parasite Trypanosoma brucei brucei; the causative agent of sleeping sickness.
KW  - dereplication
KW  - secondary metabolomics
KW  - anti-trypanosoma
KW  - Actinokineospora
KW  - Spheciospongia vagabunda
KW  - actinosporins
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119876
SN  - 1660-3397
VL  - 12
IS  - 3
ER  - 
TY  - JOUR
A1  - Macintyre, Lynsey
A1  - Zhang, Tong
A1  - Viegelmann, Christina
A1  - Martinez, Ignacio Juarez
A1  - Cheng, Cheng
A1  - Dowdells, Catherine
A1  - Abdelmohsen, Usama Ramadan
A1  - Gernert, Christine
A1  - Hentschel, Ute
A1  - Edrada-Ebel, RuAngelie
T1  - Metabolomic Tools for Secondary Metabolite Discovery from Marine Microbial Symbionts
JF  - Marine Drugs
N2  - Marine invertebrate-associated symbiotic bacteria produce a plethora of novel secondary metabolites which may be structurally unique with interesting pharmacological properties. Selection of strains usually relies on literature searching, genetic screening and bioactivity results, often without considering the chemical novelty and abundance of secondary metabolites being produced by the microorganism until the time-consuming bioassay-guided isolation stages. To fast track the selection process, metabolomic tools were used to aid strain selection by investigating differences in the chemical profiles of 77 bacterial extracts isolated from cold water marine invertebrates from Orkney, Scotland using liquid chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) spectroscopy. Following mass spectrometric analysis and dereplication using an Excel macro developed in-house, principal component analysis (PCA) was employed to differentiate the bacterial strains based on their chemical profiles. NMR H-1 and correlation spectroscopy (COSY) were also employed to obtain a chemical fingerprint of each bacterial strain and to confirm the presence of functional groups and spin systems. These results were then combined with taxonomic identification and bioassay screening data to identify three bacterial strains, namely Bacillus sp. 4117, Rhodococcus sp. ZS402 and Vibrio splendidus strain LGP32, to prioritize for scale-up based on their chemically interesting secondary metabolomes, established through dereplication and interesting bioactivities, determined from bioassay screening.
KW  - multivariate analysis
KW  - metabolic profiling
KW  - metabolomics
KW  - dereplication
KW  - symbiotic bacteria
KW  - mass spectrometry
KW  - NMR
KW  - sponge holicolona-simulans
KW  - bryozoan bugula-neritina
KW  - polyketide synthase gene
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116097
SN  - 1660-3397
VL  - 12
IS  - 6
ER  -