New Cytotoxic Secondary Metabolites from Two Deep‐Sea‐Derived Fungi and the Co‐Culture Impact on the Secondary Metabolic Patterns

Abstract

In this study, chemical profiles for two co‐existing deep‐sea‐derived Penicillium fungal strains were thoroughly investigated. Two new compounds and 11 known compounds were identified from Penicillium sp. LXY140‐R, while one new compound and 12 known compounds were isolated from Penicillium sp. LXY140‐3. Their structures were elucidated by extensive 1D and 2D NMR experiments, which were supported by HR‐ESI‐MS data. The antiproliferative activities of all isolates against HCT‐116, A549 and Bel‐7402 cell lines were also evaluated. Compounds 2, 5, 6, 10 and 13 showed potent antiproliferative activity. To reveal the metabolic relationship of the two strains, we conducted co‐culture experiments to discover cross‐talk molecules by a device that allows only small molecule to communicate. Extensive HPLC/MS2 experiments were applied to identify the disturbance of the chemical profiles within the synthetic Penicillium‐Penicillium community. The fungal strain LXY140‐R was found to accumulate mono or multiple‐acetylation derivatives of deoxynivalenol (DON) sesquiterpenes as responsible molecules by the disturbance of the metabolites produced by the LXY140‐3 strain.

Novel Bioactive Natural Products from Marine-Derived Penicillium Fungi: A Review (2021–2023)

“…The HPLC-MS/MS analyses [9], one-pot/two-stage precursor-directed biosynthesis approach [88], and molecular networks of MS/MS data generated with Global Natural Products Social Molecular Networking (GNPS) [13] have expanded the scope of research on metabolites, especially trace components of marine-derived Penicillium fungi. Co-culture [66,97,100,107] and OSMAC [17,18,20,111] have been used to explore the structural diversity of secondary metabolites from the fungi. Further research on the known compounds, whether penicopeptide A as a candidate compound for osteoporosis prevention [12] or the anti-pancreatic cancer activity of dicitrinone G evaluated using a mouse model [11], provides an opportunity to diversify the targets, increasing the value of natural products from marine-derived Penicillium fungi.…”

“…(2S,3S,5S,6S,7S,8R,11S,12R)-15-deacetyl-7,8dihydroxycalonectrin (334) and 1-methyl-4-[3,4,5-trihydroxy-1,2,2-trimethylcyclopently] benzene (335) (Figure 7) were isolated from the deep-sea-derived Penicillium sp. LXY140-R. 1-methyl-4-[3,4,5-trihydroxy-1,2,2-trimethylcyclopently] benzene (335) showed potent antiproliferative activity against HCT-116 cell lines with an IC 50 value of 124.12 µM [97]. Nor-bisabolane derivative enantiomers (±)-1 (336a/b) (Figure 7) were isolated from the algal-derived P. chrysogenum LD-201810 [98].…”

“…LXY140-3 co-culturing with Penicillium sp. LXY140-R [97]. 6-acetyl-4-methoxy-3,5-dimethyl-2H-pyran-2-one (433) and (2E,4E)-5-((2S, 3S,4R,5R)-3,4-dihydroxy-2,4,5-trimethyltetrahydrofuran-2-yl)-2,4-dimethylpenta-2,4dienal (434) (Figure 10) were identified from the mangrove-derived P. polonicum H175, and they showed no hypoglycemic effect by the Tg (Ins: htBidTE-ON; LR) zebrafish [122].…”

Marine natural products

“…237 The decahydrofluorene alkaloids pyrrospirones K–Q 733– 739 were isolated from a soft coral-derived Penicillium strain and of these, 733 and 734 possessed a 6/5/6/8/5/6/13 polycyclic skeleton whilst 735 and 736 possessed a 6/5/6/5/6/13 polycyclic skeleton. 238 Co-culture of two deep-sea-derived Penicillium strains resulted in isolation of sesquiterpenes 740 and 741 from one strain and organic acid 742 from the other 239 and other sediment-derived Penicillium strains were the source of meroterpenoid 743 (ref. 240) and alkaloids 744 , 745 , 240 746 , 747 .…”

Exploring Diverse Bioactive Secondary Metabolites from Marine Microorganisms Using Co-Culture Strategy

“…LXY140-3, Li et al designed a dialysis bag separation device, allowing only small molecules to penetrate. Co-culture studies showed that the LXY140-3 strain accumulated trichothecene sesquiterpenes by setting up a co-culture device [61]. For the co-cultivation of the strain, Streptomyces sp.…”