Stachybotrins G and H, Two New Phenylspirodrimane Derivatives from the Fungus Stachybotrys chartarum

• Abstract
• Introduction
• Results and Discussion
• Materials and Methods
• General experimental procedures
• Fungal strain
• Fermentation
• Extraction and isolation
• Spectroscopic data
• Antibacterial activity
• Contributorsʼ Statement
• References

Abstract

Two new phenylspirodrimane derivatives, designated as stachybotrins G and H (1 and 2), which feature an N-isobutyl side chain, along with four known analogues (3−6), were isolated from the fungus Stachybotrys chartarum. All the structures were determined through comprehensive spectroscopic analyses, primarily based on HRESIMS and NMR data. The antibacterial activity of all isolated compounds was evaluated. Compound 5 demonstrated antibacterial activity against the Gram-positive bacterium Staphylococcus aureus ATCC 6538, with a minimum inhibitory concentration (MIC) value of 6.25 µg/mL.

Introduction

Phenylspirodrimanes are a type of meroterpenoid composed of a common drimane-type sesquiterpene skeleton fused with a benzene ring via a spirofuran [1]. To date, more than 120 compounds of this class, including monomers and structurally diverse phenylspirodrimane dimers, have been discovered from the genera Stachybotrys and Memnoniella [1], [2], [3], since the first phenylspirodrimane K-76 was isolated from the culture broth of Stachybotrys complementi, nov. sp [4]. Members of phenylspirodrimane have been reported to possess diverse biological activities, such as antiviral [5], [6], antibacterial [7], [8], cytotoxicity [9], [10], and α-glucosidase inhibitory activity [11].

Research indicates that Stachybotrys chartarum predominantly thrives in terrestrial humid environments [12], though studies have also reported its isolation from marine sponges [5], [13]. Previous phytochemical studies on this species have led to the isolation of various types of secondary metabolites, including trichothecenes [14], diterpenoids [15], cochlioquinones [16], xanthones [17], and phenylspirodrimanes [18]. Among them, phenylspirodrimanes represent the most extensively reported class of compounds, with 114 distinct phenylspirodrimanes reported to date [19], such as stachybotrylactone acetate [18], stachybotrydial [20], and bistachybotrysins L – V [21]. As part of our program aimed at searching for novel phenylspirodrimanes, the fungus S. chartarum was fermented. The chemical investigation of the extract of S. chartarum led to the isolation of two new phenylspirodrimane derivatives, named stachybotrins G and H (1 and 2), along with four known analogues (3−6) ([Fig. 1]). Herein, the isolation, structure elucidation, and antibacterial activities of 1 and 2 are described.

Results and Discussion

The molecular formula of stachybotrin G (1) was determined to be C₂₇H₃₉NO₄ based on the HRESIMS peak at m/z 442.2955 [M + H]⁺ (calcd for C₂₇H₄₀NO₄, 442.2952), corresponding to 9 degrees of unsaturation. The ¹H NMR spectrum revealed the presence of one aromatic signals singlet [δ _H 6.68 (1H, s, H-3′)], one oxymethine signal [δ _H 3.34 (1H, m, H-3)], and six methyl signals [δ _H 1.06 (3H, s, H-15); 0.98 (9H, m, H-13, H-11′, H-12′); 0.89 (3H, s, H-14); 0.74 (3H, d, J = 6.4 Hz, H-12)]. Analysis of ¹³C NMR and HSQC spectra indicated 27 carbon resonances, corresponding to six methyls (δ _C 29.0, 23.7, 23.0, 21.5, 16.6, and 16.0), seven methylenes (δ _C 45.9, 39.9, 32.6, 32.2, 26.1, 25.4, and 22.1), five methines (δ _C 102.1, 76.4, 41.5, 38.5, and 26.5), five nonprotonated aromatic carbons (δ _C 157.6, 155.1, 134.9, 118.9, and 114.7), three quaternary carbons (δ _C 99.7, 43.5, and 38.6), and one carbonyl carbon (δ _C 171.8). The above NMR data of 1 ([Table 1]) resembled those of stachybotramide [18]. The primary difference between 1 and stachybotramide was the presence of an N-isobutyl group in 1 instead of an N-ethyl alcohol group, as in stachybotramide (7) ([Fig. 2]). The presence of an N-isobutyl group was evidenced by the HMBC correlations from H-9′β (δ _H 1.88) to the carbonyl carbon at δ _C 171.8 (C-7′) and H¹-H¹ COSY correlations from H-9′/H-10′, H-10′/H-11′, H-10′/H-12′ ([Fig. 3]).

The relative configuration of compound 1 was deduced from the ROESY spectrum. The ROESY correlations of H-3/H₃-14, H₃-14/H₃-15, H₃-15/H-8, and H₃-15/H-11β indicated that H-3, H-8, H₃-15, and H₂-11 were β-oriented. The ROESY correlation of H-5/H₃-13 revealed that the relative configurations of H-5 were α-oriented ([Fig. 3]). The ROESY spectrum of 1 indicated the same relative configuration as those of the reported compound stachybotrylactam (3).

Therefore, the structure of 1 was identified as shown in [Fig. 1]. Although many N-side chain groups of phenylspirodrimanes have been reported [5], [10], [22], this is the first instance of such compounds with N-isobutyl groups being reported. No biosynthetic reports were found for the N-side chain in phenylspirodrimanes; we identified biosynthesis reports for compounds containing similar N-side chain groups. For instance, Maddah demonstrated through [2-¹³C]sodium acetate isotope labeling experiments that the hydroxyethyl side chain of mariline B (8) ([Fig. 2]) was successfully labeled. The authors proposed that [2-¹³C]sodium acetate undergoes metabolism via the tricarboxylic acid (TCA) cycle to generate doubly labeled precursors (e.g., succinate and serine), which are subsequently incorporated into mariline B [23]. Furthermore, during the characterization of the cichorine biosynthetic gene cluster, Sanchez identified an AN11921 gene annotated as an amino acid transporter that may participate in N-side chain biosynthesis [24]. Additionally, studies on calipyridone A (9) ([Fig. 2]) biosynthesis confirmed that its N-side chain originates from a tryptophan precursor [25]. Based on the aforementioned evidence, we hypothesize that the N-side chain in phenylspirodrimanes may be derived from multiple amino acid precursors, while the N-isobutyl group reported herein is proposed to originate from valine.

The molecular formula of stachybotrin H (2) was determined to be C₃₁H₄₃NO₇ according to the HRESIMS peak at m/z 542.3110 [M + H]⁺ (calcd for C₃₁H₄₄NO₇, 542.3112), corresponding to 11 degrees of unsaturation. The ¹H NMR spectrum revealed the presence of one aromatic signals singlet [δ _H 6.74 (1H, s, H-3′)], two oxymethine signals [δ _H 5.24 (1H, m, H-2); 4.95 (1H, d, J = 1.5, H-3)], two acetoxy methyl signals [δ _H 2.11 (3H, s, OAc-3); 1.87 (3H, s, OAc-2)], and six methyl signals [δ _H 1.17 (3H, s, H-15); 1.07 (3H, s, H-14); 1.01 (3H, d, J = 0.9 Hz, H-11′); 1.00 (3H, br s, H-12′), 0.94 (3H, s, H-13); 0.83 (3H, d, J = 6.5 Hz, H-12)]. Analysis of ¹³C NMR and HSQC spectra indicated 31 carbon resonances, corresponding to eight methyls (δ _C 28.3, 23.6, 21.9, 21.4, 21.2, 20.9, 17.1, and 15.8), six methylenes (δ _C 45.4, 40.0, 32.9, 32.1, 31.5, and 21.5), six methines (δ _C 102.6, 78.3, 69.6, 41.8, 37.6, and 26.5), five nonprotonated aromatic carbons (δ _C 157.2, 155.4, 135.0, 118.5, and 114.4), three quaternary carbons (δ _C 99.2, 44.9, and 39.1), and three carbonyl carbons (δ _C 172.7, 172.3, and 171.5). The above NMR data of 2 were similar to those of 1 ([Table 1]), except for the presence of two additional acetoxy groups ([Fig. 1]). The positions of the two acetoxy groups were determined to be at C-2 and C-3, based on the cross-peaks from H-2 and H-3 to the corresponding carbonyl carbons at δ _C 172.3 and δ _C 172.7 in the HMBC spectrum of 2 ([Fig. 4]).

Acetylation modifications are frequently encountered in natural products, particularly among terpenoid compounds. A prominent example is observed in taxane diterpenoids, where numerous acetylated derivatives have been documented [26]. Subsequent investigations into the biosynthetic pathways of taxane diterpenoids have led to the identification of specific acetyltransferases responsible for position-selective modifications: TAX9 (C-10 acetylation) [27], TAX14 (C-9 acetylation) [27], and TAX19 (C-5 acetylation) [28], along with several other acetylation-modifying enzymes [29]. Furthermore, during investigations into the biosynthetic pathway of limonoid-type triterpenoids, researchers identified that the BAHD-family acetyltransferase L21AT mediates C-21 hydroxyl acetylation. Additionally, three acetyltransferases, L1AT, L7AT, and L21AT, were found to collaboratively participate in the biosynthesis of the triacetylated compound 1,7,21-O-acetyl protolimonid [30]. Therefore, based on the aforementioned literature review, it is suggested that the acetyl group modification in compound 2 may result from the action of acetyltransferases.

The relative configuration of compound 2 was established based on the ROESY spectrum. The ROESY correlations of H-2/H-3, H-2/H₃-15, H₃-15/H-8, and H₃-15/H-11β showed that H-2, H-3, H-8, H₃-15, and H₂-11 were β-oriented. The ROESY correlation of H-5/H₃-13 revealed that the relative configurations of H-5 were α-oriented ([Fig. 4]). The structure of 2 was finally determined as shown in [Fig. 1].

In addition to the two new phenylspirodrimane derivatives mentioned earlier, four known compounds were identified as stachybotrylactam (3) [18], stachybotrylactam acetate (4) [18], stachybotrylactone (5) [31], and stachybotrylactone acetate (6) [18].

All compounds were evaluated for their antibacterial activity against four Gram-positive bacteria and one Gram-negative bacterium. As shown in [Table 2], compounds 4 and 5 exhibited potent antibacterial activity against S. aureus ATCC 6538. Structure–activity relationship analysis revealed that the presence of OAc-3 decreased antibacterial activity (3 vs. 4, 5 vs. 6), and the presence of N-isobutyl group was also observed to reduce antibacterial activity (1 vs. 3). Moreover, the presence of the lactone group showed better inhibitory activity than the lactam group (3 vs. 5).

In summary, two new compounds, stachybotrins G and H (1 and 2), along with four known analogues (3−6), were isolated from the fungus S. chartarum. The N-isobutyl side chain present in stachybotrins G and H is a previously unidentified group in phenylspirodrimane derivatives. All compounds were evaluated for their antibacterial activity against four Gram-positive bacteria and one Gram-negative bacterium. Among them, compound 5 exhibited the best antibacterial activity against Gram-positive bacterium S. aureus ATCC 6538, with an MIC value of 6.25 µg/mL. The structural diversity and biological activities of natural phenylspirodrimane derivatives may be worthy of further studies.

Materials and Methods

General experimental procedures

Optical rotations were measured at 25 °C using an Anton Paar MCP-200 polarimeter (Anton Paar GmbH). Nuclear magnetic resonance (NMR) spectra were recorded on an Agilent DD2 600 MHz spectrometer with tetramethylsilane (TMS) as the internal standard (Agilent Technologies Inc.). High-resolution electrospray ionization mass spectra (HRESIMS) were obtained on an Agilent 1290 II ultra-high-performance liquid chromatograph (UHPLC) coupled with an Agilent 6530 Q-TOF mass spectrometer (Agilent Technologies Inc.). Analytical high-performance liquid chromatography (HPLC) was performed on an Agilent 1260 Series instrument with a diode array detector (DAD) using a Shim-pack VP-ODS column (250 × 4.6 mm, internal diameter [i. d.], 5 µm). Preparative HPLC was carried out on a Shimadzu LC-20AR equipped with a Shim-pack ODS column (20 mm × 250 mm, i. d., 10 µm, Shimadzu) and a Shimadzu SPD-20A multiple wavelength detector. Silica gel (100 – 200 and 200 – 300 mesh; Qingdao Haiyang Chemical Co., Ltd.) and Fuji ODS (40 – 63 µm) were used for column chromatography (CC). Thin-layer chromatography (TLC) plates (GF254, Qingdao Haiyang Chemical Co. Ltd.) were used for monitoring fractions. Spots were visualized under ultraviolet (UV) light and by spraying the plates with a 1% vanillin sulfuric acid solution followed by heating.

Fungal strain

The strain S. chartarum, with the code ACCC 37 494, used in this study was provided by the Agriculture Microbiological Culture Collection Center (ACCC). A voucher specimen (BRI-20240218-12545) is preserved at the Biotechnology Research Institute of Chinese Academy of Agricultural Sciences.

Fermentation

The strain S. chartarum was cultivated on potato dextrose agar (PDA) at 28 °C for one week. Then, the mycelium on the colony surface was gently collected using an autoclaved tweezer. This mycelium was used to inoculate a Petri dish (90 mm in diameter) containing 20 mL PDA medium. The cultures were incubated at 28 °C under static conditions for 14 to 21 days. For scale-up, 8 L of PDA medium (400 Petri dishes) were inoculated with the spore solution of S. chartarum and cultivated under the same conditions as those used for the small-scale fermentations.

Extraction and isolation

The medium with the fungal culture was cut into small pieces 1 cm × 1 cm and extracted with 100% methanol under ultrasonic condition (8 L × 3, 1 hour per extraction). The methanol extract was filtered, and the filtrate was concentrated under vacuum to yield a crude extract (3.2 g). This crude extract was subjected to macroporous D101 resin column chromatography and eluted with a gradient of CH₃OH/H₂O (v/v, 0 : 100, 50 : 50, 100 : 0) to obtain three fractions (Fr. 1 – 3). Fr. 3 (2.0 g) was subjected to ODS column chromatography and eluted with gradient CH₃OH/H₂O (v/v, 30 : 70, 50 : 50, 70 : 30, 80 : 20, 90 : 10, 100 : 0) to yield six subfractions (Fr. 3.1 – 3.6). Fr. 3.3 (268 mg) was purified by semi-preparative HPLC with gradient elution using CH₃CN/H₂O (v/v, 55 : 45 – 75 : 25, 30 min) containing 0.1% formic acid at the flow rate of 2.5 ml · min⁻¹ to give three subfractions (Fr. 3.3.1 – 3.3.3). Fr. 3.3.1 (20.3 mg) was purified by semi-preparative HPLC, eluting with CH₃CN/H₂O (v/v, 50 : 50, 30 min) to obtain 3 (4.6 mg, t _R = 13.4 min). Fr. 3.3.2 (77.5 mg) was purified by semi-preparative HPLC, eluting with CH₃CN/H₂O (v/v, 53 : 47, 30 min) to obtain 4 (1.3 mg, t _R = 12.3 min), and 5 (2.7 mg, t _R = 13.9 min). Fr. 3.3.3 (52.8 mg) was purified by semi-preparative HPLC, eluting with CH₃CN/H₂O (v/v, 55 : 45, 30 min) to obtain and 6 (2.1 mg, t _R = 15.5 min), 1 (1.6 mg, t _R = 17.2 min), and 2 (1.8 mg, t _R = 19.7 min).

Spectroscopic data

Stachybotrin G (1): white, amorphous solid; [α]_D ²⁵ − 92 (c 0.8, MeOH); ¹H and ¹³C NMR data (CD₃OD, see [Table 1]); HR-ESI-MS m/z 442.2955 [M + H]⁺ (calcd for C₂₇H₄₀NO₄, 442.2952).

Stachybotrin H (2): white, amorphous solid; [α]_D ²⁵ − 44 (c 1.0, MeOH); ¹H and ¹³C NMR data (CD₃OD, see [Table 1]); HR-ESI-MS m/z 542.3110 [M + H]⁺ (calcd for C₃₁H₄₄NO₇, 542.3112).

Antibacterial activity

A cell-based antimicrobial assay was conducted in 96-well microtiter plates using procedures reported previously [32]. Compounds were tested against four Gram-positive bacteria, namely S. aureus ATCC 6538, MRSA 11 646, ancomycin-sensitive E. faecium 160 119 481, and VRE 151 458 137, as well as one Gram-negative bacterium, E. coli ATCC 25 922. All experiments were carried out in triplicate.

Contributorsʼ Statement

Wang Yi: Data curation, Formal analysis, Writing – original draft. Chen Kang: Data curation, Writing – original draft. Xin Qiao: Data curation. Zhang Tao: Writing – review & editing, Project administration. Yuquan Xu: Writing – review & editing, Project administration, Funding acquisition.

Conflict of Interest

The authors declare that they have no conflict of interest.

• References

• 1 Wang A, Xu Y, Gao Y, Huang Q, Luo X, An H, Dong J. Chemical and bioactive diversities of the genera Stachybotrys and Memnoniella secondary metabolites. Phytochem Rev 2015; 14: 623-655
  PubMedSearch in Google Scholar
• 2 Ibrahim SRM, Choudhry H, Asseri AH, Elfaky MA, Mohamed SGA, Mohamed GA. Stachybotrys chartarum–a hidden treasure: Secondary metabolites, bioactivities, and biotechnological relevance. J Fungi 2022; 8: 504
  PubMedSearch in Google Scholar
• 3 Jiang M, Wu Z, Liu L, Chen S. The chemistry and biology of fungal meroterpenoids (2009–2019). Org Biomol Chem 2021; 19: 1644-1704
  PubMedSearch in Google Scholar
• 4 Kaise H, Shinohara M, Miyazaki W, Izawa T, Nakano Y, Sugawara M, Sugiura K, Sasaki K. Structure of K-76, a complement inhibitor produced by Stachybotrys complementi nov. Sp. K-76. J Chem Soc, Chem Commun 1979; 16: 726-727
  PubMedSearch in Google Scholar
• 5 Ma X, Li L, Zhu T, Ba M, Li G, Gu Q, Guo Y, Li D. Phenylspirodrimanes with anti-HIV activity from the sponge-derived fungus Stachybotrys chartarum MXH-X73. J Nat Prod 2013; 76: 2298-2306
  PubMedSearch in Google Scholar
• 6 Zhao J, Feng J, Tan Z, Liu J, Zhao J, Chen R, Xie K, Zhang D, Li Y, Yu L, Chen X, Dai J. Stachybotrysins A–G, phenylspirodrimane derivatives from the fungus Stachybotrys chartarum . J Nat Prod 2017; 80: 1819-1826
  PubMedSearch in Google Scholar
• 7 Wu B, Oesker V, Wiese J, Malien S, Schmaljohann R, Imhoff JF. Spirocyclic drimanes from the marine fungus Stachybotrys sp. strain MF347. Mar Drugs 2014; 12: 1924-1938
  CrossrefPubMedSearch in Google Scholar
• 8 Liu D, Li Y, Guo X, Ji W, Lin W. Chartarlactams Q−T, dimeric phenylspirodrimanes with antibacterial and antiviral activities. Chem Biodivers 2020; 17: e2000170
  PubMedSearch in Google Scholar
• 9 Zhao J, Feng J, Tan Z, Liu J, Zhang M, Chen R, Xie K, Chen D, Li Y, Chen X, Dai J. Bistachybotrysins A–C, three phenylspirodrimane dimers with cytotoxicity from Stachybotrys chartarum . Bioorg Med Chem Lett 2018; 28: 355-359
  PubMedSearch in Google Scholar
• 10 Zhang H, Yang MH, Zhuo FF, Gao N, Cheng XB, Wang XB, Pei YH, Kong LY. Seven new cytotoxic phenylspirodrimane derivatives from the endophytic fungus Stachybotrys chartarum . RSC Adv 2019; 9: 3520-3531
  PubMedSearch in Google Scholar
• 11 Wang S, Li S, Chen Y, Wang Y, Liu Z, Zhang W, Deng H. A new phenylspirodrimane derivative from the deep-sea-derived fungus Stachybotrys chartarum FS705. Nat Prod Res 2024; 39: 1-7
  PubMedSearch in Google Scholar
• 12 Jarvis BB. Stachybotrys chartarum: a fungus for our time. Phytochemistry 2003; 64: 53-60
  PubMedSearch in Google Scholar
• 13 Li Y, Wu C, Liu D, Proksch P, Guo P, Lin W. Chartarlactams A–P, phenylspirodrimanes from the sponge-associated fungus Stachybotrys chartarum with antihyperlipidemic activities. J Nat Prod 2014; 77: 138-147
  PubMedSearch in Google Scholar
• 14 Li Y, Liu D, Cheng Z, Proksch P, Lin W. Cytotoxic trichothecene-type sesquiterpenes from the sponge-derived fungus Stachybotrys chartarum with tyrosine kinase inhibition. RSC Adv 2017; 7: 7259-7267
  PubMedSearch in Google Scholar
• 15 Li YF, Zhang PP, Yan SJ, Xu JY, Niaz SI, Chand R, Eddie Ma CH, Lin YC, Li J, Liu L. Atranones with enhancement neurite outgrowth capacities from the crinoid-derived fungus stachybotrys chartarum 952. Tetrahedron 2017; 73: 7260-7266
  PubMedSearch in Google Scholar
• 16 Yoganathan K, Yang LK, Rossant C, Huang Y, Ng S, Butler MS, Buss AD. Cochlioquinones and epi-cochlioquinones: Antagonists of the human chemokine receptor CCR5 from Bipolaris brizae and Stachybotrys chartarum. J Antibiot 2004; 57: 59-63
  PubMedSearch in Google Scholar
• 17 Yang B, Long J, Pang X, Lin X, Liao S, Wang J, Zhou X, Li Y, Liu Y. Structurally diverse polyketides and phenylspirodrimanes from the soft coral-associated fungus Stachybotrys chartarum SCSIO41201. J Antibiot 2021; 74: 190-198
  PubMedSearch in Google Scholar
• 18 Jarvis BB, Salemme J, Morais A. Stachybotrys toxins. 1. Nat Toxins 1995; 3: 10-16
  PubMedSearch in Google Scholar
• 19 Ibrahim SRM, Choudhry H, Asseri AH, Elfaky MA, Mohamed SGA, Mohamed GA. Stachybotrys chartarum–a hidden treasure: Secondary metabolites, bioactivities, and biotechnological relevance. J Fungi 2022; 8: 504
  PubMedSearch in Google Scholar
• 20 Sakai K, Watanabe K, Masuda K, Tsuji M, Hasumi K, Endo A. Isolation, characterization and biological activities of novel triprenyl phenols as pancreatic cholesterol esterase inhibitors produced by Stachybotrys sp. F-1839. J Antibiot 1995; 48: 447-456
  PubMedSearch in Google Scholar
• 21 Liu J, Jia X, Zhao J, Feng J, Chen M, Chen R, Xie K, Chen D, Li Y, Zhang D, Peng Y, Si S, Dai J. Bistachybotrysins L–V, bioactive phenylspirodrimane dimers from the fungus Stachybotrys chartarum . Org Chem Front 2020; 7: 531-542
  PubMedSearch in Google Scholar
• 22 Vázquez MJ, Vega A, Rivera-Sagredo A, Jiménez-Alfaro MD, Díez E, Hueso-Rodríguez JA. Novel sesquiterpenoids as tyrosine kinase inhibitors produced by Stachybotrys chortarum . Tetrahedron 2004; 60: 2379-2385
  PubMedSearch in Google Scholar
• 23 El Maddah F, Eguereva E, Kehraus S, König GM. Biosynthetic studies of novel polyketides from the marine sponge-derived fungus Stachylidium sp. 293K04. Org Biomol Chem 2019; 17: 2747-2752
  PubMedSearch in Google Scholar
• 24 Sanchez JF, Entwistle R, Corcoran D, Oakley BR, Wang CCC. Identification and molecular genetic analysis of the cichorine gene cluster in Aspergillus nidulans . Medchemcomm 2012; 3: 997-1002
  PubMedSearch in Google Scholar
• 25 Guo Y, Contesini FJ, Wang X, Ghidinelli S, Tornby DS, Andersen TE, Mortensen UH, Larsen TO. Biosynthesis of calipyridone A represents a fungal 2-pyridone formation without ring expansion in Aspergillus californicus . Org Lett 2022; 24: 804-808
  PubMedSearch in Google Scholar
• 26 Shi QW, Kiyota H. New natural taxane diterpenoids from Taxus species since 1999. Chem Biodivers 2005; 2: 1597-1623
  PubMedSearch in Google Scholar
• 27 Hampel D, Mau CJD, Croteau RB. Taxol biosynthesis: Identification and characterization of two acetyl CoA: Taxoid-O-acetyl transferases that divert pathway flux away from taxol production. Arch Biochem Biophys 2009; 487: 91-97
  PubMedSearch in Google Scholar
• 28 Chau M, Walker K, Long R, Croteau R. Regioselectivity of taxoid-O-acetyltransferases: Heterologous expression and characterization of a new taxadien-5α-ol-O-acetyltransferase. Arch Biochem Biophys 2004; 430: 237-246
  PubMedSearch in Google Scholar
• 29 Jiang B, Gao L, Wang H, Sun Y, Zhang X, Ke H, Liu S, Ma P, Liao Q, Wang Y, Wang H, Liu Y, Du R, Rogge T, Li W, Shang Y, Houk KN, Xiong X, Xie D, Huang S, Lei X, Yan J. Characterization and heterologous reconstitution of Taxus biosynthetic enzymes leading to baccatin III. Science 2024; 383: 622-629
  PubMedSearch in Google Scholar
• 30 De La Peña R, Hodgson H, Liu JCT, Stephenson MJ, Martin AC, Owen C, Harkess A, Leebens-Mack J, Jimenez LE, Osbourn A, Sattely ES. Complex scaffold remodeling in plant triterpene biosynthesis. Science 2023; 379: 361-368
  PubMedSearch in Google Scholar
• 31 Zhang P, Li Y, Jia C, Lang J, Niaz SI, Li J, Yuan J, Yu J, Chen S, Liu L. Antiviral and anti-inflammatory meroterpenoids: Stachybonoids A–F from the crinoid-derived fungus Stachybotrys chartarum 952. RSC Adv 2017; 7: 49910-49916
  PubMedSearch in Google Scholar
• 32 Xiao D, Zhang M, Wu P, Li T, Li W, Zhang L, Yue Q, Chen X, Wei X, Xu Y, Wang C. Halovirs I–K, antibacterial and cytotoxic lipopeptaibols from the plant pathogenic fungus Paramyrothecium roridum NRRL 2183. J Antibiot 2022; 75: 247-257
  PubMedSearch in Google Scholar

Correspondence

Publication History

Received: 16 February 2025

Accepted after revision: 16 April 2025

Accepted Manuscript online:
22 April 2025

Article published online:
14 May 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

• References

• 1 Wang A, Xu Y, Gao Y, Huang Q, Luo X, An H, Dong J. Chemical and bioactive diversities of the genera Stachybotrys and Memnoniella secondary metabolites. Phytochem Rev 2015; 14: 623-655
  PubMedSearch in Google Scholar
• 2 Ibrahim SRM, Choudhry H, Asseri AH, Elfaky MA, Mohamed SGA, Mohamed GA. Stachybotrys chartarum–a hidden treasure: Secondary metabolites, bioactivities, and biotechnological relevance. J Fungi 2022; 8: 504
  PubMedSearch in Google Scholar
• 3 Jiang M, Wu Z, Liu L, Chen S. The chemistry and biology of fungal meroterpenoids (2009–2019). Org Biomol Chem 2021; 19: 1644-1704
  PubMedSearch in Google Scholar
• 4 Kaise H, Shinohara M, Miyazaki W, Izawa T, Nakano Y, Sugawara M, Sugiura K, Sasaki K. Structure of K-76, a complement inhibitor produced by Stachybotrys complementi nov. Sp. K-76. J Chem Soc, Chem Commun 1979; 16: 726-727
  PubMedSearch in Google Scholar
• 5 Ma X, Li L, Zhu T, Ba M, Li G, Gu Q, Guo Y, Li D. Phenylspirodrimanes with anti-HIV activity from the sponge-derived fungus Stachybotrys chartarum MXH-X73. J Nat Prod 2013; 76: 2298-2306
  PubMedSearch in Google Scholar
• 6 Zhao J, Feng J, Tan Z, Liu J, Zhao J, Chen R, Xie K, Zhang D, Li Y, Yu L, Chen X, Dai J. Stachybotrysins A–G, phenylspirodrimane derivatives from the fungus Stachybotrys chartarum . J Nat Prod 2017; 80: 1819-1826
  PubMedSearch in Google Scholar
• 7 Wu B, Oesker V, Wiese J, Malien S, Schmaljohann R, Imhoff JF. Spirocyclic drimanes from the marine fungus Stachybotrys sp. strain MF347. Mar Drugs 2014; 12: 1924-1938
  CrossrefPubMedSearch in Google Scholar
• 8 Liu D, Li Y, Guo X, Ji W, Lin W. Chartarlactams Q−T, dimeric phenylspirodrimanes with antibacterial and antiviral activities. Chem Biodivers 2020; 17: e2000170
  PubMedSearch in Google Scholar
• 9 Zhao J, Feng J, Tan Z, Liu J, Zhang M, Chen R, Xie K, Chen D, Li Y, Chen X, Dai J. Bistachybotrysins A–C, three phenylspirodrimane dimers with cytotoxicity from Stachybotrys chartarum . Bioorg Med Chem Lett 2018; 28: 355-359
  PubMedSearch in Google Scholar
• 10 Zhang H, Yang MH, Zhuo FF, Gao N, Cheng XB, Wang XB, Pei YH, Kong LY. Seven new cytotoxic phenylspirodrimane derivatives from the endophytic fungus Stachybotrys chartarum . RSC Adv 2019; 9: 3520-3531
  PubMedSearch in Google Scholar
• 11 Wang S, Li S, Chen Y, Wang Y, Liu Z, Zhang W, Deng H. A new phenylspirodrimane derivative from the deep-sea-derived fungus Stachybotrys chartarum FS705. Nat Prod Res 2024; 39: 1-7
  PubMedSearch in Google Scholar
• 12 Jarvis BB. Stachybotrys chartarum: a fungus for our time. Phytochemistry 2003; 64: 53-60
  PubMedSearch in Google Scholar
• 13 Li Y, Wu C, Liu D, Proksch P, Guo P, Lin W. Chartarlactams A–P, phenylspirodrimanes from the sponge-associated fungus Stachybotrys chartarum with antihyperlipidemic activities. J Nat Prod 2014; 77: 138-147
  PubMedSearch in Google Scholar
• 14 Li Y, Liu D, Cheng Z, Proksch P, Lin W. Cytotoxic trichothecene-type sesquiterpenes from the sponge-derived fungus Stachybotrys chartarum with tyrosine kinase inhibition. RSC Adv 2017; 7: 7259-7267
  PubMedSearch in Google Scholar
• 15 Li YF, Zhang PP, Yan SJ, Xu JY, Niaz SI, Chand R, Eddie Ma CH, Lin YC, Li J, Liu L. Atranones with enhancement neurite outgrowth capacities from the crinoid-derived fungus stachybotrys chartarum 952. Tetrahedron 2017; 73: 7260-7266
  PubMedSearch in Google Scholar
• 16 Yoganathan K, Yang LK, Rossant C, Huang Y, Ng S, Butler MS, Buss AD. Cochlioquinones and epi-cochlioquinones: Antagonists of the human chemokine receptor CCR5 from Bipolaris brizae and Stachybotrys chartarum. J Antibiot 2004; 57: 59-63
  PubMedSearch in Google Scholar
• 17 Yang B, Long J, Pang X, Lin X, Liao S, Wang J, Zhou X, Li Y, Liu Y. Structurally diverse polyketides and phenylspirodrimanes from the soft coral-associated fungus Stachybotrys chartarum SCSIO41201. J Antibiot 2021; 74: 190-198
  PubMedSearch in Google Scholar
• 18 Jarvis BB, Salemme J, Morais A. Stachybotrys toxins. 1. Nat Toxins 1995; 3: 10-16
  PubMedSearch in Google Scholar
• 19 Ibrahim SRM, Choudhry H, Asseri AH, Elfaky MA, Mohamed SGA, Mohamed GA. Stachybotrys chartarum–a hidden treasure: Secondary metabolites, bioactivities, and biotechnological relevance. J Fungi 2022; 8: 504
  PubMedSearch in Google Scholar
• 20 Sakai K, Watanabe K, Masuda K, Tsuji M, Hasumi K, Endo A. Isolation, characterization and biological activities of novel triprenyl phenols as pancreatic cholesterol esterase inhibitors produced by Stachybotrys sp. F-1839. J Antibiot 1995; 48: 447-456
  PubMedSearch in Google Scholar
• 21 Liu J, Jia X, Zhao J, Feng J, Chen M, Chen R, Xie K, Chen D, Li Y, Zhang D, Peng Y, Si S, Dai J. Bistachybotrysins L–V, bioactive phenylspirodrimane dimers from the fungus Stachybotrys chartarum . Org Chem Front 2020; 7: 531-542
  PubMedSearch in Google Scholar
• 22 Vázquez MJ, Vega A, Rivera-Sagredo A, Jiménez-Alfaro MD, Díez E, Hueso-Rodríguez JA. Novel sesquiterpenoids as tyrosine kinase inhibitors produced by Stachybotrys chortarum . Tetrahedron 2004; 60: 2379-2385
  PubMedSearch in Google Scholar
• 23 El Maddah F, Eguereva E, Kehraus S, König GM. Biosynthetic studies of novel polyketides from the marine sponge-derived fungus Stachylidium sp. 293K04. Org Biomol Chem 2019; 17: 2747-2752
  PubMedSearch in Google Scholar
• 24 Sanchez JF, Entwistle R, Corcoran D, Oakley BR, Wang CCC. Identification and molecular genetic analysis of the cichorine gene cluster in Aspergillus nidulans . Medchemcomm 2012; 3: 997-1002
  PubMedSearch in Google Scholar
• 25 Guo Y, Contesini FJ, Wang X, Ghidinelli S, Tornby DS, Andersen TE, Mortensen UH, Larsen TO. Biosynthesis of calipyridone A represents a fungal 2-pyridone formation without ring expansion in Aspergillus californicus . Org Lett 2022; 24: 804-808
  PubMedSearch in Google Scholar
• 26 Shi QW, Kiyota H. New natural taxane diterpenoids from Taxus species since 1999. Chem Biodivers 2005; 2: 1597-1623
  PubMedSearch in Google Scholar
• 27 Hampel D, Mau CJD, Croteau RB. Taxol biosynthesis: Identification and characterization of two acetyl CoA: Taxoid-O-acetyl transferases that divert pathway flux away from taxol production. Arch Biochem Biophys 2009; 487: 91-97
  PubMedSearch in Google Scholar
• 28 Chau M, Walker K, Long R, Croteau R. Regioselectivity of taxoid-O-acetyltransferases: Heterologous expression and characterization of a new taxadien-5α-ol-O-acetyltransferase. Arch Biochem Biophys 2004; 430: 237-246
  PubMedSearch in Google Scholar
• 29 Jiang B, Gao L, Wang H, Sun Y, Zhang X, Ke H, Liu S, Ma P, Liao Q, Wang Y, Wang H, Liu Y, Du R, Rogge T, Li W, Shang Y, Houk KN, Xiong X, Xie D, Huang S, Lei X, Yan J. Characterization and heterologous reconstitution of Taxus biosynthetic enzymes leading to baccatin III. Science 2024; 383: 622-629
  PubMedSearch in Google Scholar
• 30 De La Peña R, Hodgson H, Liu JCT, Stephenson MJ, Martin AC, Owen C, Harkess A, Leebens-Mack J, Jimenez LE, Osbourn A, Sattely ES. Complex scaffold remodeling in plant triterpene biosynthesis. Science 2023; 379: 361-368
  PubMedSearch in Google Scholar
• 31 Zhang P, Li Y, Jia C, Lang J, Niaz SI, Li J, Yuan J, Yu J, Chen S, Liu L. Antiviral and anti-inflammatory meroterpenoids: Stachybonoids A–F from the crinoid-derived fungus Stachybotrys chartarum 952. RSC Adv 2017; 7: 49910-49916
  PubMedSearch in Google Scholar
• 32 Xiao D, Zhang M, Wu P, Li T, Li W, Zhang L, Yue Q, Chen X, Wei X, Xu Y, Wang C. Halovirs I–K, antibacterial and cytotoxic lipopeptaibols from the plant pathogenic fungus Paramyrothecium roridum NRRL 2183. J Antibiot 2022; 75: 247-257
  PubMedSearch in Google Scholar

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