Antibacterial Polyketides from the Deep-Sea Cold-Seep-Derived Fungus Talaromyces sp. CS-258.

Thirty-two fungal polyketide derivatives, including eleven new compounds, namely (3 R ,5' R )-5-hydroxytalaroflavone ( 1 ), talaroisochromenols A-C ( 3 , 5 , and 11 ), (8 R ,9 R ,10a R )-5-hydroxyaltenuene ( 13 ), (8 R ,9 R ,10a S )-5-hydroxyaltenuene ( 14 ), (8 R ,9 S ,10a R )-5-hydroxyaltenuene ( 15 ), nemanecins D and E ( 25 and 26 ), 2,5-dimethyl-8-iodochromone ( 27 ), and talarofurolactone A ( 29 ), together with one new naturally occurring but previously synthesized metabolite, 6-hydroxy-4-methoxycoumarin ( 28 ), were isolated and identified from the deep-sea cold-seep-derived fungus Talaromyces sp. CS-258. Among them, racemic ((±)- 11 ) or epimeric ( 13 - 15 , 25 , and 26 ) mixtures were successfully separated by chiral or gradient elution HPLC. Meanwhile, compound 27 represents a rarely reported naturally occurring iodinated compound. Their planar structures as well as absolute configurations were determined by extensive analysis via NMR, MS, single-crystal X-ray diffraction, Mosher's method, and ECD or NMR calculation (with DP4 + probability analysis). Possible biosynthetic routes of some isolated compounds, which are related to chromone or isochromone biosynthetic pathways, were put forward. The biological analysis results revealed that compounds 7 , 9, 10, 18 - 22 , 24 , 30 , and 31 showed broad-spectrum antibacterial activities against several human and aquatic pathogens with MIC ranges of 0.5-64 μg/mL.