Discovery of Unusual Cyanobacterial Tryptophan-Containing Anabaenopeptins by MS/MS-Based Molecular Networking

Abstract

Heterocytous cyanobacteria are among the most prolific sources of bioactive secondary metabolites, including anabaenopeptins (APTs). A terrestrial filamentous Brasilonema sp. CT11 collected in Costa Rica bamboo forest as a black mat, was studied using a multidisciplinary approach: genome mining and HPLC-HRMS/MS coupled with bioinformatic analyses. Herein, we report the nearly complete genome consisting of 8.79 Mbp with a GC content of 42.4%. Moreover, we report on three novel tryptophan-containing APTs; anabaenopeptin 788 (1), anabaenopeptin 802 (2), and anabaenopeptin 816 (3). Furthermore, the structure of two homologues, i.e., anabaenopeptin 802 (2a) and anabaenopeptin 802 (2b), was determined by spectroscopic analysis (NMR and MS). Both compounds were shown to exert weak to moderate antiproliferative activity against HeLa cell lines. This study also provides the unique and diverse potential of biosynthetic gene clusters and an assessment of the predicted chemical space yet to be discovered from this genus.

Polyene Macrolactams from Marine and Terrestrial Sources: Structure, Production Strategies, Biosynthesis and Bioactivities

“…Remarkably, many studies used the genomic prescience of natural products to choose the prioritization of feature response data for further isolation. A wide variety of statistical and analytical techniques based on algorithms of machine learning combined with visualized response map was applied to improve prioritization, such as global natural products social molecular networking (GNPS) and MS-based visualizing techniques [85][86][87]. With the assistance of genomic analysis [88] and predicting potential drug candidates from organisms and monitoring metabolites and mapping analysis of metabolomics via liquid chromatography-mass spectrometry (LC-MS)/MS [53,72], the known metabolites were identified and excluded.…”

Fatty Acid Substitutions Modulate the Cytotoxicity of Puwainaphycins/Minutissamides Isolated from the Baltic Sea Cyanobacterium Nodularia harveyana UHCC-0300

“…Crude extracts were prepared following the pre-established protocol. , Briefly, freeze-dried biomass was ground with the sea sand and extracted three times with 75% MeOH in water, followed by bath sonication. The extracts were evaporated under vacuum using a rotary vacuum evaporator (Heidolph, Germany) and dissolved with 75% MeOH in water to get a final concentration of 4 mg/mL for LC–MS/MS analysis.…”

Anabaenopeptins from Cyanobacteria in Freshwater Bodies of Greece

“…Anabaenopeptins (APs) are cyanobacterial metabolites with a cyclic peptide structure [1]. The presence of APs has been reported in freshwater [2][3][4][5][6] and marine cyanobacterial blooms [7][8][9], as well as in terrestrial environments, including the leaves of plants in a coastal forest [10] and the terrestrial mat in a bamboo forest [11]. APs are produced by freshwater, marine and terrestrial cyanobacteria [12] mainly belonging to the genera Planktothrix [13,14], Anabaena [15][16][17][18], Microcystis [19][20][21][22][23] and Nostoc [24,25].…”

“…[52] and Brasilonema sp. [11] are known APs producers. APs are also produced by symbiotic cyanobacteria that have been isolated from the marine sponges Theonella sp.…”