Isolation and Antibiotic Screening of Fungi from a Hydrothermal Vent Site and Characterization of Secondary Metabolites from a <Emphasis Type="Italic">Penicillium</Emphasis> Isolate

Five new compounds were isolated from Penicillium sp. Y-5-2 including an austin derivative 4, four isocoumarins 9, 11, 12, and 13, together with two known isocoumarins 8 and 10, and six known austin derivatives 1, 2, 3, 5, 6, and 7 and one phenol 14. Their structures and relative configurations were established by spectroscopic means. The absolute configurations of 4, 11, and 13 were defined mainly by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. The cyclization of the pentan-2-ol pendant at C-3 in compound 13 allowed the assignment of a new 2,3,4,4a,6,10b-hexahydro-1H-benzo[c]chromene isocoumarin skeleton. New compounds 9, 11, and 13 revealed inhibitory activities against E. coli at MIC values around 32 μg/mL. The known compound 14 showed potent antibiotic activity against Staphylococcus aureus and Bacillus subtilis with MIC values 8 and 2 μg/mL, respectively, with no cytotoxicity when tested in vitro. A rapid and efficient technique for selecting antibiotic fungal strain among eight marine-derived fungi was also described.     

Stress-driven discovery of a cryptic antibiotic produced by Streptomyces sp. WU20 from Kueishantao hydrothermal vent with an integrated metabolomics strategy

Marine hydrothermal microorganisms respond rapidly to the changes in the concentrations and availability of metals within hydrothermal vent microbial habitats which are strongly influenced by elevated levels of heavy metals. Most hydrothermal vent actinomycetes possess a remarkable capability for the synthesis of a broad variety of biologically active secondary metabolites. Major challenges in the screening of these microorganisms are to activate the expression of cryptic biosynthetic gene clusters and the development of technologies for efficient dereplication of known compounds. Here, we report the identification of a novel antibiotic produced by Streptomyces sp. WU20 isolated from the metal-rich hydrothermal vents in Taiwan Kueishantao, following a strategy based on metal induction of silent genes combined with metabolomics analytical methods. HPLC-guided isolation by tracking the target peak resulted in the characterization of the novel compound 1 with antimicrobial activity against Bacillus subtilis. The stress metabolite 1 induced by nickel is structurally totally different compared with the normally produced compounds. This study underlines the applicability of metal induction combined with metabolic analytical techniques in accelerating the exploration of novel antibiotics and other medically relevant natural products.