Albocycline Is the Main Bioactive Antifungal Compound Produced by Streptomyces sp. OR6 against Verticillium dahliae.

Verticillium wilt is a soil-borne fungal disease that affects olive trees (Olea europaea) and poses a serious threat to their cultivation. The causal agent of this disease is Verticillium dahliae, a pathogen that is difficult to control with conventional methods. Therefore, there is a need to explore alternative strategies for the management of Verticillium wilt. In this study, we aimed to isolate and characterize actinobacteria from the rhizosphere of olive trees that could act as potential biocontrol agents against V. dahliae. We selected a Streptomyces sp. OR6 strain based on its in vitro antifungal activity and its ability to suppress the pathogen growth in soil samples. We identified the main active compound produced by this strain as albocycline, a macrolide polyketide with known antibacterial properties and some antifungal activity. Albocycline was able to efficiently suppress the germination of conidiospores. To our knowledge, this is the first report of albocycline as an effective agent against V. dahliae. Our results suggest that Streptomyces sp. OR6, or other albocycline-producing strains, could be used as a promising tool for the biological control of Verticillium wilt.

Anthraquinones as Inhibitors of SOS RAS-GEF Activity.

Recent breakthroughs have reignited interest in RAS GEFs as direct therapeutic targets. To search for new inhibitors of SOS GEF activity, a repository of known/approved compounds (NIH-NACTS) and a library of new marine compounds (Biomar Microbial Technologies) were screened by means of in vitro RAS-GEF assays using purified, bacterially expressed SOS and RAS constructs. Interestingly, all inhibitors identified in our screenings (two per library) shared related chemical structures belonging to the anthraquinone family of compounds. All our anthraquinone SOS inhibitors were active against the three canonical RAS isoforms when tested in our SOS GEF assays, inhibited RAS activation in mouse embryonic fibroblasts, and were also able to inhibit the growth of different cancer cell lines harboring WT or mutant RAS genes. In contrast to the commercially available anthraquinone inhibitors, our new marine anthraquinone inhibitors did not show in vivo cardiotoxicity, thus providing a lead for future discovery of stronger, clinically useful anthraquinone SOS GEF blockers.