1. Exploration of Chemical Diversity and Antitrypanosomal Activity of Some Red Sea-Derived Actinomycetes Using the OSMAC Approach Supported by LC-MS-Based Metabolomics and Molecular Modelling
Ahmed O El-Gendy, Yara I Shamikh, Usama Ramadan Abdelmohsen, Noha M Gamaleldin, Hossam M Hassan, Walid Bakeer, Ahmed M Sayed, Hannes Horn, Wael N Hozzein Antibiotics (Basel) . 2020 Sep 22;9(9):629. doi: 10.3390/antibiotics9090629.
In the present study, we investigated the actinomycetes associated with the Red Sea-derived soft coralSarcophyton glaucumin terms of biological and chemical diversity. Three strains were cultivated and identified to be members of generaMicromonospora,Streptomyces, andNocardiopsis; out of them,Micromonosporasp. UR17 was putatively characterized as a new species. In order to explore the chemical diversity of these actinobacteria as far as possible, they were subjected to a series of fermentation experiments under altering conditions, that is, solid and liquid fermentation along with co-fermentation with a mycolic acid-containing strain, namelyNocardiasp. UR23. Each treatment was found to affect these actinomycetes differently in terms of biological activity (i.e., antitrypanosomal activity) and chemical profiles evidenced by LC-HRES-MS-based metabolomics and multivariate analysis. Thereafter, orthogonal projections to latent structures discriminant analysis (OPLS-DA) suggested a number of metabolites to be associated with the antitrypanosomal activity of the active extracts. The subsequent in silico screenings (neural networking-based and docking-based) further supported the OPLS-DA results and prioritized desferrioxamine B (3), bafilomycin D (10), and bafilomycin A1 (11) as possible antitrypanosomal agents. Our approach in this study can be applied as a primary step in the exploration of bioactive natural products, particularly those from actinomycetes.
2. A unique indolizinium alkaloid streptopertusacin A and bioactive bafilomycins from marine-derived Streptomyces sp. HZP-2216E
Zhizhen Zhang, Weiyun Chai, Xiao-Yuan Lian, Xiufang Zhang, Lu Chen Phytochemistry . 2017 Dec;144:119-126. doi: 10.1016/j.phytochem.2017.09.010.
Streptopertusacin A, a unique indolizinium alkaloid existing as a zwitterion, and six bafilomycins including two previously undescribed ones of 21,22-en-bafilomycin D and 21,22-en-9-hydroxybafilomycin D were isolated from a culture of the seaweed-derived Streptomyces sp. HZP-2216E. Structures of these isolated compounds were determined based on extensive NMR spectroscopic analyses, HRESIMS and MS-MS data. The stereochemical assignments were achieved by NOE information, chemical degradation, Marfey's method, and electronic circular dichroism (ECD) calculation. Streptopertusacin A is the first example of this type of indolizinium alkaloid from microorganisms and showed moderate activity against the growth of methicillin-resistant Staphylococcus aureus (MRSA). 21,22-en-bafilomycin D and 21,22-en-9-hydroxybafilomycin D had potent activities in inhibiting the proliferation of glioma cells and the growth of MRSA.
3. Hygrobafilomycin, a cytotoxic and antifungal macrolide bearing a unique monoalkylmaleic anhydride moiety, from Streptomyces varsoviensis
Heinz-Herbert Fiebig, Christian Hertweck, Klaus-Dieter Menzel, Isabel Sattler, Armin Maier, Basile Le S Tchize Ndejouong, Gerhard Kelter J Antibiot (Tokyo) . 2010 Jul;63(7):359-63. doi: 10.1038/ja.2010.52.
A new bafilomycin-type macrolide, named hygrobafilomycin (6), was isolated by a bioassay-guided selection and fractionation from a terrestrial actinomycete, Streptomyces varsoviensis, along with three known derivatives, bafilomycin D (3), C1 (4) and C2 (5). The structure of hygrobafilomycin was fully established by MS and NMR analyses, revealing a hygrolidin-bafilomycin hybrid with an unusual monoalkylmaleic anhydride moiety. Hygrobafilomycin (6) shows strong antifungal, antiproliferative and cytotoxic activities. In a panel of 40 tumor cell lines, compound 6 shows high cytotoxic potency (mean IC(50)=5.3 n).