Bio-Guided Isolation of Antimalarial Metabolites from the Coculture of Two Red Sea Sponge-Derived Actinokineospora and Rhodococcus spp.

Abstract

Coculture is a productive technique to trigger microbes’ biosynthetic capacity by mimicking the natural habitats’ features principally by competition for food and space and interspecies cross-talks. Mixed cultivation of two Red Sea-derived actinobacteria, Actinokineospora spheciospongiae strain EG49 and Rhodococcus sp. UR59, resulted in the induction of several non-traced metabolites in their axenic cultures, which were detected using LC–HRMS metabolomics analysis. Antimalarial guided isolation of the cocultured fermentation led to the isolation of the angucyclines actinosporins E (1), H (2), G (3), tetragulol (5) and the anthraquinone capillasterquinone B (6), which were not reported under axenic conditions. Interestingly, actinosporins were previously induced when the axenic culture of the Actinokineospora spheciospongiae strain EG49 was treated with signalling molecule N-acetyl-d-glucosamine (GluNAc); this finding confirmed the effectiveness of coculture in the discovery of microbial metabolites yet to be discovered in the axenic fermentation with the potential that could be comparable to adding chemical signalling molecules in the fermentation flask. The isolated angucycline and anthraquinone compounds exhibited in vitro antimalarial activity and good biding affinity against lysyl-tRNA synthetase (PfKRS1), highlighting their potential developability as new antimalarial structural motif.

The Nexus between Fire and Soil Bacterial Diversity in the African Miombo Woodlands of Niassa Special Reserve, Mozambique

“…Actinokineospora was differentially more abundant in OH. This genus constitutes a promising source of a wide range of bioactive compounds of pharmaceutical interest [ 106 , 107 , 108 , 109 ]. Zavarzinella is likely involved in the degradation of organic matter [ 110 ] and Microlunatus, a strong candidate to manage environmental pollution [ 111 ], was differentially abundant in RL, while Pirellula , a potential indicator of desertification [ 112 ], and Virgisporangium , of yet unknown function, were more abundant in RH.…”

Natural Products from Actinomycetes Associated with Marine Organisms

“…UK-2B (75) with antifungal activity was isolated from the axenic cultures of strain EG49. And the separate cultivation of strain UR59 leads to the identification of Mitomycin K (antitumor activity) (76), Piericidin F (anticancer activity) (77), Migrastatin (anticancer activity) (78) (Figure 2) [59].…”

“…Tetrangulol was also reported as an antibiotic in previous research. What's more, the separate cultivation of strain UR59 leads to the isolation of Kaimonolide B (166) (Figure 6) (plant growth inhibitor) and 8,15-Dideoxylankanolide (S78) [59]. Microluside A (148) (Figure 6) is a unique O-glycosylated disubstituted xanthone separated from Micrococcus sp.…”

Stress Driven Discovery of Natural Products From Actinobacteria with Anti-Oxidant and Cytotoxic Activities Including Docking and ADMET Properties

“…Thanks to the improvement of molecular biology and chemical biology techniques that imply that abiotic factors such as heavy metals may switch the production of natural compounds by modifying the attitude of secondary metabolism. The secondary metabolites produced by modern techniques like genome sequencing [ 7 ], abiotic or biotic stress [ 8 ], co-culture [ 9 ] and biosynthetic engineering proved to have enhanced pharmacological profiles compared to the compounds produced by the normal lab culture. Natural products have played an essential role in pharmacological and nutraceutical development [ 10 , 11 , 12 ]…”