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Distachydrimanes A–F, phenylspirodrimane dimers and hybrids with cytotoxic activity from the coral-derived fungus Stachybotrys chartarum
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Shuang Lin1, Jianzheng Huang1, Hanxiao Zeng, Qingyi Tong*, Xueke Zhang, Beiye Yang, Ying Ye, Jianping Wang, Zhengxi Hu*, Yonghui Zhang*
Chinese Chemical Letters | 2022, 33(10) : 4587 - 4594
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Chinese Chemical Letters | 2022, 33(10): 4587-4594
• Communication •
Distachydrimanes A–F, phenylspirodrimane dimers and hybrids with cytotoxic activity from the coral-derived fungus Stachybotrys chartarum
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Shuang Lin1, Jianzheng Huang1, Hanxiao Zeng, Qingyi Tong*, Xueke Zhang, Beiye Yang, Ying Ye, Jianping Wang, Zhengxi Hu*, Yonghui Zhang*
Affiliations
  • Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Published: 2022-10-15 doi: 10.1016/j.cclet.2022.03.064
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By integrating one strain-many compounds (OSMAC) and LC–MS-based molecular networking strategies, distachydrimanes A–F (1–6), six novel phenylspirodrimane dimers and hybrids representing two types of unprecedented terpenoid-polyketide hybrid skeletons, were isolated from the modified fermented rice substrate of a coral-derived fungus Stachybotrys chartarum. All the structures incorporating their absolute configurations were elucidated based on comprehensive spectroscopic analyses, mainly including HRESIMS and NMR data, single-crystal X-ray diffraction (Cu Kα), and comparison of the experimental electronic circular dichroism (ECD) data. Architecturally, compounds 1–6 represent an unprecedented class of dimeric phenylspirodrimanes with an unexpected C-18–C-23′ linkage, of which compounds 1–3 also feature an unexpected 5-methyl-1, 3-benzenediol moiety via a carbon-carbon linkage. The bioactivity assay demonstrated that compounds 1, 5 and 6 induced cell proliferation inhibition, G0/G1 cell cycle arrest, senescence and mitochondrial-mediated apoptosis in L1210 cells, highlighting their potentials as a new category of anticancer agents.

Stachybotrys chartarum  /  Distachydrimanes A–F  /  Structure elucidation  /  Cytotoxic activity  /  Mechanism of action
Shuang Lin, Jianzheng Huang, Hanxiao Zeng, Qingyi Tong, Xueke Zhang, Beiye Yang, Ying Ye, Jianping Wang, Zhengxi Hu, Yonghui Zhang. Distachydrimanes A–F, phenylspirodrimane dimers and hybrids with cytotoxic activity from the coral-derived fungus Stachybotrys chartarum[J]. Chinese Chemical Letters, 2022 , 33 (10) : 4587 -4594 . DOI: 10.1016/j.cclet.2022.03.064
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Cancer poses the greatest incidence and mortality rate worldwide. It was caused by an abnormal cell growth with the ability to invade and spread throughout the organism [1], accounting for an estimated 10 million deaths in 2020 [2]. It is estimated that over the next 20 years, cancer cases are predicted to increase by 60% globally and by up to 81% in low- and middle-income countries [3]. More than that, the current clinical cancer treatments are still faced with recurrence due to the residual cancer cells and minute lesions in surgery, chemotherapy and other treatments [4]. Therefore, there is an urgent need to develop novel drugs for cancer therapy.
Natural products (NPs), isolated from plants, microbes, and even animals, are an immense reservoir of bioactive molecules that play an irreplaceable role in the discovery and development of innovative drugs [5-7]. NPs are thought to have ushered a new golden age since the 2015 Nobel Prize in Physiology or Medicine was awarded to avermectin and artemisinin [8]. Drugs developed from NPs have been confirmed to possess many beneficial pharmacological effects and are widely used to treat various human diseases [9, 10], for cancer therapy, such as taxol [11] and doxorubicin [12] are successful precedents.
In recent years, our research team has performed several studies towards chemically novel and bioactive secondary metabolites from fungi inhabiting unique environments [13-18], and a coral-derived fungus Stachybotrys chartarum came into our sight. Previously, we have isolated and identified six new dolabellanes and atranones from the title fungus [19]. To tap into the fungus-stored biosynthetic potentials, we adopted the OSMAC strategy by adding 0.1% Fe2(SO4)3 and 3% sea salt into the normal rice medium and employed LC–MS/MS–GNPS (Global Natural Product Social Molecular Networking) data to analyze the metabolites. By screening against GNPS spectral database (Fig. 1), four nodes (parent ions at m/z 429.218, 471.240, 387.217 and 371.139) were identified as stachybotrysin C [20], stachybotrysin H [21], stachybotrylactone [22], and mer-NF5003E [23], respectively, which have been isolated and characterized from the Stachybotrys species as potential leads for anticancer, antivirus, anti-inflammatory, and avian myeloblastosis virus protease inhibitor drugs. These analytical data suggested the presence of more bioactive phenylspirodrimane congeners in the metabolites of fungus S. chartarum, which stimulated us to ulteriorly investigate this fungus by a large-scale culture [24], facilitating the isolation and characterization of six novel phenylspirodrimane dimers and hybrids, namely distachydrimanes A–F (1–6). Structurally, compounds 1–6 represent a series of skeletally unprecedented dimeric phenylspirodrimanes via an unexpected C-18–C-23′ linkage, of which compounds 1–3 are uniquely defined by an unexpected 5-methyl-1, 3-benzenediol moiety via a carbon-carbon linkage. Additionally, all six compounds showed certain cytotoxic activity, and notably compounds 5 and 6 showed significant cytotoxic activity against all cancer cell lines (< 10 µmol/L). Herein, the detailed isolation, structure elucidation, cytotoxic activity and the preliminary mechanism of these compounds are described.
Strain S. chartarum was cultured on potato dextrose agar (PDA) plates at 28 ℃ for 7 days to prepare the seed cultures. Agar plugs were cut into small pieces (approximately 0.2 × 0.2 × 0.2 cm3) and inoculated into 400 Erlenmeyer flasks (1 L), previously sterilized by autoclaving, each containing 250 g of rice and 250 mL of distilled water (adding 0.1% Fe2(SO4)3 and 3% sea salt). All flasks were incubated at 28 ℃ for 30 days. The growth of fungus was stopped by adding 250 mL of 95% EtOH to each flask, and the solvent was decanted and removed under reduced pressure. The rice cultures were soaked with the recycled EtOH five times until the solvent extract was nearly colorless at room temperature. The concentrated extract was suspended in water (3 L) and extracted with EtOAc (1:1, v/v) three times to obtain a total residue of 400 g.
The EtOAc residue was fractionated on RP-C18 silica gel CC eluted with MeOH–H2O (20%, 40%, 50%, 60%, 80%, and 100%) to give four main fractions (A–D). Fraction B (MeOH–H2O, 60:40, v/v) was loaded onto Sephadex LH-20 (CH2Cl2–MeOH, 1:1, v/v) and silica gel CC eluted with petroleum ether–ethyl acetate (5:1, 2:1, 1:1, and 0:1, v/v) to give seven main fractions (B1–B7) by TLC analysis. Fraction B2 was subjected to RP-C18 column chromatography eluted with a step gradient of MeOH–H2O (from 20:80 to 80:20, v/v) to yield seven fractions (B2-1–B2-7) in total. Fraction B2-4 was separated by semi-preparative HPLC (MeCN–H2O, 89:11, v/v; 2.0 mL/min) to afford compound 5 (5.2 mg, tR 30.1 min). Fraction B2-5 was subjected to semi-preparative HPLC (MeOH–H2O, 88:12, v/v; 2.0 mL/min) to afford compound 4 (4.9 mg, tR 20.5 min). Fraction B5 was separated into four fractions (B5-1–B5-4) by Sephadex LH-20 eluted with CH2Cl2–MeOH (1:1, v/v). Fraction B5-1 was purified via semi-preparative HPLC (MeCN–H2O, 80:20, v/v; 2.0 mL/min) to provide compounds 2 (3.9 mg, tR 19.5 min) and 3 (2.9 mg, tR 30.5 min). Fraction B5-2 was consecutively separated by semi-preparative HPLC (MeOH–H2O, 81:19, v/v; 2.0 mL/min) to provide compound 1 (7.4 mg, tR 12.0 min). Fraction B6 was applied to Sephadex LH-20 (CH2Cl2–MeOH, 1:1, v/v) and silica gel CC eluted with petroleum ether–ethyl acetate (5:1, 3:1, 2:1, and 1:1, v/v) to obtain four main fractions (B6-1–B6-4) by TLC analysis. Fraction B6-2 (petroleum ether–ethyl acetate, 3:1, v/v) was purified via semi-preparative HPLC (MeCN–H2O, 92:8, v/v; 2.0 mL/min) to afford compound 6 (5.2 mg, tR 35.8 min).
Distachydrimane A (1) was obtained as a colorless crystal with a molecular formula of C57H72O13, as deduced from the HRESIMS data at m/z 987.4848 [M + Na]+ (calcd. for 987.4865), corresponding to 22 degrees of unsaturation. The IR spectrum of 1 showed absorption bands for hydroxy (3420 cm–1), ester carbonyl (1744 and 1719 cm–1) and double bond (1627 cm–1) groups. The 13C and DEPT NMR data (Table S2 in Supporting information) revealed 57 carbon resonances, including 11 methyl carbons, 11 methylene carbons (including two oxygenated), nine methine carbons (including five oxygenated), six quaternary carbons (including two oxygenated), 18 aromatic carbons for three phenyl groups, and two ester carbonyl carbons. Combined with the 1H NMR data (Table S1 in Supporting information) of compound 1, the typical signals including two oxygenated methylenes at δH 5.32/5.68 and 4.99/5.09 and eight methyls at δH 0.27, 0.22, 0.99, 0.87, 0.92, 1.10, 0.98, and 0.94 for a phenylspirodrimane dimer backbone were observed. Further analysis of 2D NMR data (Fig. 2) validated the presence of two structurally similar phenylspirodrimane monomers, except that two acetyl groups were respectively attached to C-2 and C-3 in unit A and only one hydroxy group was attached to C-3′ in unit B. Moreover, the essential signals were carefully assigned by the HMBC correlations from H-23′ to C-18 and C-20′ (Fig. 2), which established an unexpected C-18–C-23′ linkage between units A and B. Interestingly, an extra 4-substituted-5-methyl-1, 3-benzenediol moiety (unit C) was attached to C-23, which could be discerned by the HMBC correlations from H-23 to C-3′′/C-5′′, from H-6′′ to C-1′′/C-2′′, from OH-3′′ to C-2′′/C-3′′, and from H3-7′′ to C-4′′/C-5′′/C-6′′ (Fig. 2). Therefore, the planar structure of 1 was defined, which represents the first example of dimeric phenylspirodrimane featured by an unexpected C-18–C-23′ linkage (units A and B) and hybrid with an unusual 5-methyl-1, 3-benzenediol moiety.
The relative configuration of 1 was determined by analysis of the coupling constant and NOESY data (Fig. S1 in Supporting information). With the fact that H-3 and H-3′ of phenylspirodrimane-type sesquiterpenoids maintained the β-orientation [25], and the small coupling constant between H-2 and H-3 (J = 2.5 Hz) inferred that they were in the cis-relationship, therefore H-2, H-3 and H-3′ were all assigned to be β-oriented. The NOESY correlations of H3-13/H-2/H-3, H-2/H3-15, H3-15/H-8, H3-15/H-11b and H-8/H-11a in unit A, as well as H3-13′/H-2′β/H-3′, H-2′β/H3-15′, H3-15′/H-8′, H3-15′/H-11′b and H-8′/H-11′a in unit B, indicated that H3-13/13′, H3-15/15′, H-8/8′ and CH2-11/11′ were β-oriented just like H-2 and H-3/3′, whereas the NOESY cross-peaks of H3-14/H-5 and H3-14′/H-5′ suggested that H3-14/14′ and H-5/5′ were on the opposite side with α-orientations. These results were supportive of the common configurations at all corresponding chiral centers as reported phenylspirodrimane dimers [25]. Crucially, the diagnostic NOESY correlations of H3-14′/H-23 and H-23′/H-22a/H-22b were observed, which implied the α-orientation of H-23/23′.
Regarding the novelty and complexity of 1, we attempted recrystallization in various two-phase or three-phase solvent systems to address the issue of growing suitable crystals for X-ray diffraction experiment so as to furnish solid evidence for its structure. Fortunately, a high-quality crystal was obtained from CH2Cl2–EtOH–H2O (10:10:1), which was then successfully analyzed by single-crystal X-ray diffraction with Cu Kα radiation (Flack parameter = –0.04(6); Fig. 3). Accordingly, the absolute configuration of 1 was unambiguously determined as 2R, 3S, 5S, 8R, 9R, 10S, 23S, 3′R, 5′S, 8′R, 9′R, 10′S, 23′S.
Distachydrimane B (2) was isolated as a colorless oil. Its molecular formula was determined as C61H76O16 by the HRESIMS analysis (m/z 1087.5095 [M + Na]+, calcd for 1087.5026), indicating 24 indices of hydrogen deficiency. The 1D NMR data (Tables S1 and S2) of 2 showed high similarities to those of 1, implying that 2 was also a phenylspirodrimane dimer. The obvious differences were that a methylene (δC 24.3, C-2′) in 1 was replaced by an oxymethine (δC 68.2, C-2′) in 2 and two acetyl groups were severally connected to C-2′ and C-3′, suggesting the replacement of unit B in 1 by unit A' in 2. This assumption was further confirmed by the key 1H–1H COSY correlation of H-2′ (δH 5.24)/H-3′ (δH 5.03) and HMBC correlations as shown in Fig. 2.
Compound 2 has one more chiral center C-2′ than that of 1, and the small coupling constant between H-2′ and H-3′ (J = 2.8 Hz) implied that they were also in the cis-relationship and assigned as β-oriented (in unit A'). The NOESY cross-peaks of 2 highly resembled those of 1 as shown in Fig. S1, indicating that units A and A' in 2 possessed the same relative configurations as those of 1. The same biosynthetic pathways and closely similar ECD curves (Fig. 4) of 1 and 2 suggested the absolute configuration of 2 to be 2/2′R, 3/3′S, 5/5′S, 8/8′R, 9/9′R, 10/10′S, 23/23′S.
Distachydrimane C (3) was deduced to have a molecular formula of C61H76O16, according to the HRESIMS data (m/z 1087.5001 [M + Na]+, calcd. for 1087.5026), which was the same as that of 2. Comprehensive analysis of the NMR data (Tables S1 and S2) of 3 and 2 suggested that both compounds were structural congeners, except for the part of unit C. Two pairs of carbons with the equal chemical shifts (δC 155.1, C-1′′/3′′; δC 112.0, C-4′′/6′′) were observed on the benzene ring in unit C, suggesting the replacement of a 4-substituted-5-methyl-1, 3-benzenediol moiety in 2 by a 2-substituted-5-methyl-1, 3-benzenediol moiety in 3, which can be confirmed by the detailed 1H–1H COSY and HMBC correlations as shown in Fig. 2. The similar NOE data and ECD curves (Fig. 4) of 2 and 3 allowed an explicit assignment of the absolute configuration of 3 as 2/2′R, 3/3′S, 5/5′S, 8/8′R, 9/9′R, 10/10′S, 23R/23′S.
Distachydrimane D (4) had the molecular formula C51H68O12 with 18 indices of unsaturation, which was determined by the HRESIMS data (m/z 895.4606 [M + Na]+, calcd. for 895.4603). Analysis of the NMR data (Tables S1 and S2) of 4 suggested that it was also a phenylspirodrimane dimer and two phenylspirodrimane monomers of 4 were the same as those of 1, which could be further demonstrated by the HMBC and 1H–1H COSY correlations (Fig. 2). The only imparity was that a methoxy group (δC 51.0) linked to C-23 in 4 replaced a 4-substituted-5-methyl-1, 3-benzenediol moiety at the same position in 1, which was confirmed by the key HMBC correlation from OCH3-23 (δH 3.23) to C-23 (δC 105.5). Similar NOESY data and ECD curves (Fig. 4) of 1 and 4 suggested that both compounds shared the identical absolute configuration. To further verify this conclusion by a more reliable method, the recrystallization experiment was attempted with various two-phase or three-phase solvent systems under atmospheric conditions. Luckily, the mixed CH2Cl2–EtOH–H2O (10:10:1, v/v/v) solutions of 4 afforded crystals suitable for X-ray crystallography, and they were explicitly identified as ethoxylate 4a, which could also be supported by the evidence that a C-23 methoxy group disappeared and an ethoxy group (δH 3.72, 2H, q, J = 7.1 Hz; δH 1.23, 3H, dd, J = 7.1, 1.8 Hz) existed in 4a (Fig. S56 in Supporting information). The crystallography data [Flack parameter = –0.10(5)] demonstrated the absolute stereochemistry of 4a to be 2R, 3S, 5S, 8R, 9R, 10S, 23R, 3′R, 5′S, 8′R, 9′R, 10′S, 23′S (Fig. 3), which was identical to that of 4. Accordingly, the absolute structure of 4 was defined.
Distachydrimane E (5) was assigned to a molecular formula of C55H72O15 by the HRESIMS analysis at m/z 995.4735 [M + Na]+ (calcd. for 995.4763). The 1D NMR data (Tables S1 and S2) of 5 showed a close structural resemblance to those of 2, defining that a 4-substituted-5-methyl-1, 3-benzenediol moiety in 2 was replaced by a methoxy group (δC 51.3) linked to C-23 in 5, which was supported by the key HMBC correlation from the proton of methoxy group to C-23 (Fig. 2). The same NOESY correlations of 5 and 2 could be discernible and their ECD spectra showed similar Cotton effects (Fig. 4), which suggested the absolute configuration of 5 could also be assigned as 2/2′R, 3/3′S, 5/5′S, 8/8′R, 9/9′R, 10/10′S, 23R/23′S.
Distachydrimane F (6) was deduced as a C-23 epimer of 5 from their identical HRESIMS ion peaks and awfully similar 1D NMR data (Tables S1 and S2), except that the discernible signals C-23 (δC 107.5) and OCH3-23 (δC 56.4) of 6 were distinguished from C-23 (δC 105.6) and OCH3-23 (δC 51.3) of 5. Crucially, the diagnostic NOESY correlation of the methoxy proton (δH 3.51) to H3-14′ further verified the S-configuration of C-23 in 6 (Fig. S1). The absolute configurations of all other chiral centers were deduced to be the same as those of 5 (2R, 3S, 5S, 8R, 9R, 10S, 2′R, 3′S, 5′S, 8′R, 9′R, 10′S, 23′S) by comparing their identical NOESY correlations and ECD curves (Fig. 4).
Distachydrimanes A–F (1–6) represent two special classes of dimeric phenylspirodrimanes with unprecedented carbon skeletons. Their plausible biosynthetic pathways are proposed as follows (Scheme 1). A series of phenylspirodrimane monomers including stachybotrysin C, stachybotrysin H, and mer-NF5003E, are derived from orsellinic acid and farnesyl diphosphate (FPP) through key prenylation, cyclization, and redox reactions [26]. Further hydroxylation, methylation and dehydration reactions afford intermediates i and ii, which undergo a further Friedel-crafts reaction via an unexpected C-18–C-23′ bond to generate an intermediate iii. Selective acetylation of rings A/A' of iii could create compounds 4–6. On the other hand, after the removal of methoxy, iii undergoes a key Friedel-crafts reaction with a small molecule orcinol via a carbon-carbon linkage, and further oxidation and acetylation reactions to produce compounds 1–3.
The bioactivity of compounds 1–6 against seven cancer cell lines was initially assessed by a CCK-8 kit, and etoposide (VP16) was used as the positive control. Compounds 5 and 6 showed significant anti-proliferation effect against all cancer cell lines, with IC50 values ranging from 2.66 µmol/L to 8.14 µmol/L, and compounds 1, 3 and 4 also showed remarkable anti-proliferation effect against most of these cancer cell lines, especially to L1210 (Table S3 in Supporting information; Figs. 5A–C). Regarding the yield and novelty of these chemical structures, compounds 1, 5 and 6 were chosen to further explore the anti-proliferation effect and mechanism of this kind of compounds. We first detected the signaling of S6 ribosomal protein, which is a marker of cell proliferation, mitogenic stimulation and overexpressed in various cancers [27]. Compounds 1, 5 and 6 treatments showed no effect on S6, but significantly inhibited its phosphorylated form after 24 h, and even a complete inhibition was found after compound 1 treatment for 48 h (Fig. 5D). These results demonstrated that the proliferation inhibition effects of compounds 1, 5 and 6 were associated with the down-regulation of S6 phosphorylation. Moreover, cell morphological changes were very obvious. Microscopic imaging showed that, after compounds 1, 5 and 6 treatments, some cells shrank and became dense, and some cells featured cytoplasmic swelling and plasma membrane bubbles featured classic apoptotic bodies (Fig. 5E), suggesting that these compounds probably induced apoptosis.
Thus, we performed the apoptosis assays. The induction of apoptosis was first evaluated by DAPI nuclear staining, and the results indicated that compounds 1, 5 and 6 treatments induced significant stronger blue stain, which labeled the internucleosome fragmentation of genomic DNA during apoptosis (Fig. 6A). Apoptosis was further detected and quantified by Annexin V-FITC/PI staining kit and flow cytometer. Compounds 1, 5 and 6 (10, 10 and 5 µmol/L, respectively), treated for 48 h caused 78.9%, 82.6% and 48.6% apoptosis in L1210 cells, respectively (Fig. 6B). To further explore the mechanism of apoptosis induction effect of compounds 1, 5 and 6, the mitochondrial membrane potential (MMP) of L1210 cells was evaluated. As shown in Fig. 6C, compounds 1, 5 and 6 (especially 1 and 5) treatments decreased MMP of L1210 cells, suggesting that mitochondria may be involved in their apoptotic induction effect. In order to confirm this, proteins of Bcl-2 family as well as the cleaved-caspase 3, PARP were detected. As shown in Fig. 6D, treatments of compounds 1, 5 and 6 altered the expression levels of PARP, cleaved-caspase 3, Bcl-XL and Bax. The DNA damage marker γ-H2AX also sharply increased after treated with compounds 1, 5 and 6. Taken together, these data suggested that compounds 1, 5 and 6 induced mitochondrial-mediated apoptosis in L1210 cells.
Cell proliferation, DNA damage and apoptosis are closely related to the cell cycle. Our results showed that compounds 1, 5 and 6 treated for 24 h induced G0/G1 arrest in L1210 cells (Figs. 7A and B). As arrest in the G0/G1 phase of cell cycle has been considered as a marker of senescent cells [28], we next detected cellular senescence with SA-β-gal staining in L1210 cells treated with compounds 1, 5 and 6 in low concentrations, and all of them induced cellular senescence (Fig. 7C). At the molecular level, treatments of 1, 5 and 6 up-regulated the expression levels of checkpoint proteins involved in the regulation of the G1/S transition including cyclin D2, CDK2 and CDK6, and also up-regulated the expression levels of p16, p21 and p53, which are major upstream regulators of the G1/S cell–cycle checkpoint and cellular senescence (Fig. 7D) [29]. The above data suggested that compounds 1, 5 and 6 induced G0/G1 arrest and senescence in L1210 cells and that p53, p21, and p16 may involve in this process. Taken together, compounds 1, 5 and 6 inhibited proliferation, induced G0/G1 cell cycle arrest, senescence and mitochondria-mediated apoptosis in L1210 cells.
In conclusion, uncovered by the OSMAC and LC–MS-based molecular networking strategies, six novel phenylspirodrimane dimers and hybrids (1–6) were isolated and characterized from a modified large-scale culture of a coral-derived fungus S. chartarum. Structurally, compounds 1–6 represent a series of skeletally unprecedented dimeric phenylspirodrimanes by an unexpected linkage between C-18 and C-23′, simultaneously compounds 1–3 are uniquely defined by an unexpected 5-methyl-1, 3-benzenediol moiety via a carbon-carbon linkage. The mechanism of action investigation revealed that compounds 1, 5 and 6 induced cell proliferation inhibition, G0/G1 phase cell cycle arrest and senescence, leading to mitochondria-mediated apoptosis in L1210 cells. Our current findings provide two novel classes of phenylspirodrimane dimers and hybrids as promising candidate molecules for hematological leukemia treatment research.
Declaration of competing interest
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The authors have no conflicts of interest to declare.
Acknowledgments
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We thank the Analytical and Testing Center at Huazhong University of Science and Technology for measuring ECD, IR, UV and single-crystal X-ray diffraction data. This project was financially supported by the National Natural Science Foundation for Distinguished Young Scholars (No. 81725021), the Innovative Research Groups of the National Natural Science Foundation of China (No. 81721005), the National Natural Science Foundation of China (No. 81573316), the Fundamental Research Funds for the Central Universities (Nos. 2020kfyXJJS083, 2021yjsCXCY094 and 2172019kfyXJJS166), the Tongji-Rongcheng Center for Biomedicine, Huazhong University of Science and Technology (No. 0231514141), the Research and Development Program of Hubei Province (No. 2020BCA058), and the Hubei Provincial Natural Science Foundation of China (No. 2019CFB646).
Supplementary materials
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Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.cclet.2022.03.064
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doi: 10.1016/j.cclet.2022.03.064
  • Receive Date：2021-12-01
  • Online Date：2025-12-24
  • Published：2022-10-15
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  • Received：2021-12-01
  • Revised：2022-03-14
  • Accepted：2022-03-15
Affiliations
    Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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