Integrating Taxonomic and Chemical Diversity of Mangrove-Associated Ascomycetes to Discover or Repurpose Bioactive Natural Products

Abstract

Natural product reisolation is a bottleneck when discovering new bioactive chemical entities from nature. To overcome this issue, multi-informative approaches integrating several layers of data have been applied with promising results. In this study, integration of taxonomy, nontargeted metabolomics, and bioactivity information resulted in the selection of Scytalidium sp. IQ-074 and Diaporthe sp. IQ-053 to isolate new natural products active against hPTP1B1–400 and repurpose others as antibiotics. Strain IQ-074 was selected based on the hypothesis that investigating poorly studied and highly metabolic taxa could lead to the isolation of new chemical entities. A chemical investigation of IQ-074 resulted in the isolation of papyracillic acid A (14), 7-deoxypapyracillic acid A (15a and 15b), and linear polyketides scytalpolyols A–D (16–19). Compound 17 inhibited hPTP1B1–400 with a half-maximal inhibitory concentration of 27.0 ± 1.7 μM. Diaporthe sp. IQ-053 was selected based on its antibacterial properties against pathogenic strains. Its chemical investigation yielded dothiorelones A (20) and I (21), cytosporones B (22) and C (23), pestalotiopsone B (24), and diaporthalasin (25). Compounds 22 and 25 inhibited the growth of Staphylococcus aureus and Staphylococcus epidermidis 42R and moderately inhibited the growth of Acinetobacter baumannii A564, a pandrug-resistant bacterium.

Bioactive α-Pyrone Analogs from the Endophytic Fungus Diaporthe sp. CB10100: α-Glucosidase Inhibitory Activity, Molecular Docking, and Molecular Dynamics Studies

“…The 1 H NMR spectrum (Table 1) also indicated the presence of one methyl group [δ H 2.20 (3H, s)], two methylenes [δ H 2.33 (2H, t, J = 7.4 Hz and 2.49 (m)] and two sp 2 methines [δ H 6.12 (1H, d, J = 9.3 Hz, H-3) and 7.46 (1H, d, J = 9.4 Hz, H-4)]. The 1 H and 13 C NMR data of 3 are similar to those of a previously isolated pyrone, diaporpyrone D (4), with a two-carbon aliphatic chain; one difference was the chemical shift of one carbon atom, C2 ′ (δ C 34.8), indicating the presence of an α-pyrone ring. Based on these observations, relative to diaporpyrone D (4), 3 contains one more methylene group (Table 1; Figure S2).…”

“…Cytosporone B obtained from Diaporthe sp. IQ-053 had minimum inhibitory concentration (MIC) values of 21 ± 2.6 and 18 ± 2.9 µg/mL against S. epidermidis 42R and S. aureus, respectively [13].…”

“…Cytosporone B obtained from Diaporthe sp. IQ-053 had minimum inhibitory concentration (MIC) values of 21 ± 2.6 and 18 ± 2.9 µg/mL against S. epidermidis 42R and S. aureus, respectively [13]. α-Pyrone, an aromatic unsaturated lactone, is present as a substructure in a diverse range of natural substances that exhibit noteworthy biological activities [14].…”

“…1 H NMR spectrum of 3 in DMSO-d 6 (500 MHz); FigureS2:13 C NMR spectrum of 3 in DMSO-d 6 (125 MHz); Figure S3: DEPT-90 spectrum of 3; Figure S4: DEPT-135 spectrum of 3; Figure S5: HSQC spectrum of 3; Figure S6: HMBC spectrum of 3; Figure S7: 1 H-1 H COSY spectrum of 3; Figure S8: NOESY spectrum of 3; Figure S9: HRESIMS spectrum of 3; Figure S10: UV spectrum of 3; Figure S11: 1 H NMR spectrum of 4 in DMSO-d 6 (600 MHz); Figure S12: 13 C NMR spectrum of 4 in DMSO-d 6 (150 MHz); Figure S13: DEPT-135 spectrum of 4; Figure S14: HSQC spectrum of 4; Figure S15: HMBC spectrum of 4; Figure S16: 1 H-1 H COSY spectrum of 4; Figure S17: HRESIMS spectrum of 4; Figure S18: UV spectrum of 4; Figure S19: Structures of diaporpyrones A-D (S1-S4) isolated from endophilic fungus strain Diaporthe sp. CB10100; Figure S20: Docking poses and interactions of acarbose with α-glucosidase (PDB ID: 2QMJ); Figure S21: 96 well plate assay of 3-4 against MRSA (A), Mycolicibacterium (Mycobacterium) smegmatis (B) and Klebsiella pneumonia (C) using the microbroth dilution method.…”

“…The 1 H NMR (500 MHz) and13 C NMR (125 MHz) data of diaporpyrone F (3) in DMSO-d 6 (δ in ppm, J in Hz).…”