Three novel, highly oxygenated polyketides, multioketides A−C (1−3), and three previously described multioxidized aromatic polyketides (4−6), were isolated from an endophytic Penicillium sp. YUD17006 associated with Gastrodia elata. Their chemical structures were elucidated using extensive spectroscopic data, electronic circular dichroism calculations, and single X-ray diffraction analysis. All metabolites were characterized by a typical α,β-unsaturated ketone fragment and exhibited a high degree of oxidation. Multioketides A and B were identified as a pair of epimers featuring a rare dihydroisobenzofuranone core. Multioketide C possessed a novel 5/6/6/6 heterotetracyclic chemical architecture with unusual 1,4-dioxin functionalities. Plausible biosynthetic pathways for 1−6 were proposed. Additionally, compound 3 demonstrated weak inhibitory activities against both acetylcholinesterase and protein tyrosine phosphatase 1B.
| [1] |
Wright GD. Opportunities for natural products in 21st century antibiotic discovery[J]. Nat Prod Rep, 2017, 34(7): 694-701.
|
| [2] |
Crawford J, Korman T, Labonte J, et al. Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization[J]. Nature, 2009, 461(7267): 1139-1143.
|
| [3] |
Truax NJ, Romo D. Bridging the gap between natural product synthesis and drug discovery[J]. Nat Prod Rep, 2020, 37(11): 1436-1453.
|
| [4] |
Newman DJ, Cragg GM. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019[J]. J Nat Prod, 2020, 83(3): 770-803.
|
| [5] |
Zang Y, Gong Y, Shi Z, et al. Multioxidized aromatic polyketides produced by a soil-derived fungus Penicillium canescens[J]. Phytochemistry, 2022, 193: 113012.
|
| [6] |
Lin Z, Phadke S, Lu Z, et al. Onydecalins, fungal polyketides with anti-histoplasma and anti-TRP activity[J]. J Nat Prod, 2018, 81(12): 2605-2611.
|
| [7] |
Li X, Chen HP, Zhou L, et al. Cordycicadins A-D, antifeedant polyketides from the entomopathogenic fungus Cordyceps cicadae JXCH1[J]. Org Lett, 2022, 24(47): 8627-8632.
|
| [8] |
Lin J, Liu S, Sun B, et al. Polyketides from the ascomycete fungus Leptosphaeria sp.[J]. J Nat Prod, 2010, 73(5): 905-910.
|
| [9] |
Ding WY, Yan YM, Meng XH, et al. Isolation, total synthesis, and absolute configuration determination of renoprotective dimeric N-acetyldopamine-adenine hybrids from the insect Aspongopus chinensis[J]. Org Lett, 2020, 22(15): 5726-5730.
|
| [10] |
Li HT, Yang RN, Liu T, et al. Fungal polyketides from a rhizospheric soil-derived Penicillium sp. YUD17004 associated with Gastrodia elata[J]. Phytochemistry, 2023, 205: 113475.
|
| [11] |
Li HT, Tang L, Liu T, et al. Polyoxygenated meroterpenoids and a bioactive illudalane derivative from a co-culture of Armillaria sp. and Epicoccum sp. [J]. Org Chem Front, 2019, 6(23): 3847-3853.
|
| [12] |
Li HT, Zhou H, Duan RT, et al. Inducing secondary metabolite production by co-culture of the endophytic fungus Phoma sp. and the symbiotic fungus Armillaria sp. [J]. J Nat Prod, 2019, 82(4): 1009-1013.
|
| [13] |
Li HT, Sun Y, Xie F, et al. Xanthene and citrinin derivatives from the endophytic fungus Penicillium sp. T2-11[J]. Tetrahedron Lett, 2022, 90: 153626.
|
| [14] |
Trana TD, Wilson BAP, Henrich CJ, et al. Structure elucidation and absolute configuration of metabolites from the soil-derived fungus Dictyosporium digitatum using spectroscopic and computational methods[J]. Phytochemistry, 2020, 173: 112278.
|
| [15] |
Pescitelli G, Bruhn T. Good computational practice in the assignment of absolute configurations by TDDFT calculations of ECD spectra[J]. Chirality, 2016, 28(6): 466-474.
|
| [16] |
Zang Y, Gong YH, Li XW, et al. Canescones A-E: aromatic polyketide dimers with PTP1B inhibitory activity from Penicillium canescens[J]. Org Chem Front, 2019, 6(18): 3274-3281.
|
| [17] |
Ying YM, Zhang LW, Shan WG, et al. Secondary metabolites of Peyronellaea sp. XW-12, an endophytic fungus of Huperzia serrata[J]. Chem Nat Compd, 2014, 50: 723-725.
|
| [18] |
Varma GB, Fatope MO, Marwah RG, et al. Production of phenylacetic acid derivatives and 4-epiradicinol in culture by Curvularia lunata[J]. Phytochemistry, 2006, 67: 1925-1930.
|
| [19] |
Singh SB, Zink DL, Quamina DS, et al. Integrastatins: structure and HIV-1 integrase inhibitory activities of two novel racemic tetracyclic aromatic heterocycles produced by two fungal species[J]. Tetrahedron Lett, 2002, 43: 2351-2354.
|
| [20] |
Tshitenge DT, Feineis D, Awale S, et al. Gardenifolins A-H, scalemic neolignans from Gardenia ternifolia: chiral resolution, configurational assignment, and cytotoxic activities against the HeLa cancer cell line[J]. J Nat Prod, 2017, 80(5): 1604-1614.
|
| [21] |
Zang Y, Gong Y, Gong J, et al. Fungal polyketides with three distinctive ring skeletons from the fungus Penicillium canescens uncovered by OSMAC and molecular networking strategies[J]. J Org Chem, 2020, 85(7): 4973-4980.
|
| [22] |
Xie FZ, Yang FZ, Liang YY, et al. Investigation of stereoisomeric bisarylethenesulfonic acid esters for discovering potent and selective PTP1B inhibitors[J]. Eur J Med Chem, 2019, 164: 408-422.
|
| [23] |
Gerlach SL, Dunlop RA, Metcalf JS, et al. Cyclotides chemosensitize glioblastoma cells to temozolomide[J]. J Nat Prod, 2022, 85(1): 34-46.
|
| [24] |
Shao M, Sun C, Liu X, et al. Upregulation of a marine fungal biosynthetic gene cluster by an endobacterial symbiont[J]. Commun Biol, 2020, 3(1): 527.
|
| [25] |
Sun L, Li W, Li J, et al. Uncommon diterpenoids from the south China sea soft coral Sinularia humilis and their stereochemistry[J]. J Org Chem, 2021, 86(4): 3367-3376.
|
| [26] |
Ellman GL, Courtney KD, Andres V, et al. A new and rapid colorimetric determination of acetylcholinesterase activity[J]. Biochem Pharmacol, 1961, 7(2): 88-95.
|
Funding
Natural Science Foundation of China(22267001)
Program for Innovative Research Team of Yunnan Province(202105AE160006)
Science and Technology Project of Yunnan Province(202201AT070225)
Science and Technology Project of Yunnan Province(202301AU070217)
Yunnan University “Double First-Class” Construction Joint Project(202201BF070001-014)
Basic Research Plan of Yunnan Provincial Science and Technology Department-Kunming Medical University(202301AY070001-186)
Project of Yunnan Characteristic Plant Screening and R&D Service CXO Platform(2022YKZY001)
Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University(MZY2205)
Program Innovative Research Team in Science and Technology in Kunming Medical University(CXTD202202)
PDF
(870KB)
