Project's information

Project's title Research on the application of biotechnology and gene technology in searching and exploiting precious biopharmaceutical active substances (Vinblastine, Huperzia, Paclitaxel, Camptothecin, Podophyllotoxin,...) from endophytic fungi on Vietnamese medicinal plants
Project’s code TĐCNSH.00/20-22
Research hosting institution Institute of Biotechnology
Project leader’s name Prof. Dr Chu Hoang Ha
Project duration 01/01/2020 - 31/12/2023
Project’s budget 45,000 million VND
Classify Grade A
Goal and objectives of the project
- Obtain a full set of documents on plant species in Vietnam that synthesize Vinblastine, Huperzia, Paclitaxel, Camptothecin, Podophyllotoxin, and other compounds.
- Obtain a collection of endophytic fungal strains synthesizing Vinblastine, Huperzia, Paclitaxel, Camptothecin, Podophyllotoxin, and other compounds. 
- Obtain the genomic data of selected endophytic fungal strains. 
- Develop biosynthetic pathways for bioactive compounds of selected fungal strains. 
- Develop a process to isolate active ingredients from selected plant species and fungal strains.
- Establish a process to obtain the desired active ingredient from selected fungal strains.
- Evaluate the potential application of products in the treatment of serious diseases (cancer, Alzheimer's)
Main results
In terms of science:
- Collected 156 samples of 45 plant species from many provinces and cities across the country, of which 128 samples were fixed into specimens for storage. By morphological classification and/or gene sequencing methods, the group of individuals was classified into species, including Dysosma difformis, Dysosma versipellis, Catharanthus roseus L. (G.) Don, Oldenlandia corymbosa L., Ehretia asperula Zoll. et Mot., Scutellaria barbata D. Don, Crinum latifolium L., Callisia fragrans, Iodes sp., Iodes cirrhosa Turcz., Piper betle, Ixora chinensis, Ophiorrhiza japonica, Ophiorrhiza mungos, Ophiorrhiza baviensis, Lycopodiella cernua (L.) Pic. Serm., Lycopodium casuarinoides Spring., Lycopodium clavatum L., Lycopodium clavatum L., Huperzia serrata (Thunb.) Trevis., Huperzia javanica (Sw.) C. Yang., Phlegmariurus phlegmaria (L.) T.Sen & U.Sen, Phlegmariurus squarrosus (G. Forst.) Á.Löve & D.Löve), Phlegmariurus hamiltonii (Spreng.) Á.Löve & D.Löve), Phlegmariurus fordii (Baker) Ching), Phlegmariurus henryi (Baker) Ching), Amentotaxus ynnanensis H.L.Li, Taxus chinensis (Pilg.) Rehder), Cephalotaxus mannii Hook.f., Tsuga chinensis (Franch.) Pritz.), Taxus wallichiana Zucc., Rhizophoraceae mucronata Lam, Kandelia obovata Sheue, H.Y.Liu & J.Yong), Bruguiera gymnorrhiza (L.) Savigny), Avicennia marina var. rumphiana (Hall. f.) Bakh), Aegiceras corniculatum (L.) Blanco), Taxus wallichiana Zucc., Tabernaemontana bovina Lour., Gomphandra tonkinesis Gagnep., Juniperus chinensis L., Podocarpus macrophyllus (Thunb.) Sweet), Tabernaemontana corymbosa Roxb. ex Wall., Tabernaemontana langbianensis (Lý) Lý), Tabernaemontana divaricata (L.) R.Br. ex Roem. & Schult), Lycopodium clavatum L.
A total of 59 compounds from plant samples were extracted, isolated, and determined the chemical structure, 8 of which are novel compounds from Taxus wallichiana Zucc, Tabernaemontana bovina Lour, and Iodes cirrhosa Turcz, namely wallichianone A, wallichianone B, taberbovinine A, taberbovinine B, iodescirrhoside A, iodescirrhoside B, iodescirrhoside C, and iodescirrhoside D. Concurrently, the presence of taxol, camptothecin, and podophyllotoxin compounds along with their analogues/precursors including:
The pharmaceutical substance taxol and 7 similar compounds are 10-deacetyltaxol, 7-epi-10-deacetyltaxol, taxol-7-xyloside, 7-xylosyl-10-deacetyltaxol C, cephalomannine, 10-deacetylcaphalomannine, 7-epi-10-deacetylcephalomannine isolated from Taxus wallichiana Zucc 
Compounds (16S*)-15-epi-E-isositsirikine, (16R*)-15-epi-E-isositsirikine, 16R*-19,20-E-isositsirikine acetate are precursors of camptothecin isolated from Tabernaemontana bovina Lour
The compound matairesinol 4-glucopyranoside, matairesinol 4ʹ-glucopyranoside is a precursor of podophyllotoxin isolated from Juniperus chinensis L
Evaluation of the anticancer activity of plant extracts and clean compounds on 5 human epithelial cancer cell lines, including HepG2, SK-LU-1, MCF-7, SK-Mel-2, and LNCaP, showed that 4 extracts and 13 compounds exhibited anticancer activity against all tested cancer cell lines (IC50 from 1.43–94.09 µM). Compounds (16S*)-15-epi-E-isositsirikine, 14,15-dihydroxy-N-methylaspidospermidine, voafinidine showed cytotoxic activity on 3 cell lines MCF-7, SK-Mel-2, and LNCaP (IC50 from 51.67–93.37 µM). At the same time, the antimicrobial activity of the compounds from the Iodescirrhosa Turcz sample was evaluated, 10 compounds inhibited the growth of E. faecalis with MIC values of 37.5-300 µM; 5 compounds inhibited the growth of S. aureus with MIC values of 300 µM; 2 compounds inhibited the growth of B. cereus with MIC values of 150-300 µM; 5 compounds inhibited the growth of C. albicans with MIC values of 150-300 µM).
Establish the collection of 1131 endophytic fungal strains isolated from plant samples. Based on morphological characteristics and ITS gene sequences, 353 strains were classified, among which the ITS gene sequences of 96 strains were registered on Genbank. Endophytic fungal strains from medicinal plants have a great diversity in genus and species. 
Thirty-eight endophytic fungal strains were screened can cause toxicity to at least one of the cell lines such as A549 lung cancer, HeLa cervical cancer, HEPG2 liver cancer, MCF-7 breast cancer, SGC-7910 stomach cancer, A2780 ovarian cancer, K526 chronic myeloid leukemia cell line. At the same time, many endophytic fungal strains also synthesize antibiotics resistant to the tested microorganisms such as Escherichia coli (VTCC 12023), Staphylococcus aureus (VTCC 12275), Fusarium sp VTCC 31768, Bacillus cereus ATCC 11778, S. aureus ATCC 25923, methicillin-resistant S. epidermidis (MRSE) ATCC 35984, methicillin-resistant S. aureus (MRSA) ATCC 33591, Enterococcus faecalis ATCC 29212, E. coli ATCC 25922, E. coli ATCC 11105, Pseudomonas aeruginosa ATCC 27853, P. aeruginosa ATCC 9027, Candida albicans ATCC 10231
Selection of 28 strains to synthesize target compounds, specifically as follows:
5 endophytic fungal strains synthesize podophyllotoxin and derivatives, including Penicillium citrinum HGN13C, Setophoma sp. LCN13T, P. herquei HG12.1C, Fusarium proliferatum TQN5T và P. herquei TQN2L
3 vincristine/vinblastine synthase strains, including Alternaria spp. DC1, Talaromyces spp. DC2, và Cladosporium spp. DC3.
3 endophytic fungal strains can biosynthesize camptothecin, including Penicillium oxalicum I1R1, Diaporthe ampelina I2T2 và Penicillium sp. I3R2
14 strains of endophytic fungi synthesize HupA và/HupB belong to 10 different genera/species: Neurospora calospora TLC9, N. calospora TLC10, N. calospora TLC11, Schizophyllum commune TLC12, Schizophyllum sp. TLC22, Daldinia sp. TLC19, Epicoccum sorghinum TLC13, E. sorghinum THG1-18, Alternaria tenuissima TLC14, Cephalotrichum sp. TLC20, Colletotrichum siamense THG1-17; Phyllosticta sp. HG2-27; Phoma sp. TKH3-2; Aspergillus sp. TTĐ2-2.7. Strains exhibit acetylcholinesterase (AChE) inhibitory activity with IC50 values ranging from  25,10 to 134,19 µg/mL.
3 selected fungal strains able to produce paclitaxel or its derivatives, namely Fusarium foetens AQF6, Fusarium solani TQF6 và Schizophyllum commune TZT10
Sequencing, assembling, and annotating the genomes of 15 endophytic fungal strains using PacBio technology and 01 transcriptome sequence of Penicillium sp. I3R2, particularly:
P. herquei HGN12C.1, P. citrinum HGN13C, and F. proliferatum TQN5T with genome sizes of 35.0; 39.3; 47 Mb, respectively, corresponding to 98.3%; 95.8%, and 96.3% completeness.
Alternaria spp. DC1, Talaromyces spp. DC2, and Cladosporium spp. DC3 have genome sizes of 40,2; 34,5; and 39,2 Mb, respectively, corresponding to 93,3%;90,0%, and 96,9% completeness,
The genomes of P. oxalicum I1R1, D. ampelina I2T2, and Penicillium sp. I3R2 has coverage >75X and completeness >96% according to BUSCO 
Transcriptome sequencing of camptothecin-synthesizing fungus Penicillium sp. I3R2 had 89X coverage and a BUSCO score of 95%.
S. commune TLC12, Daldinia sp. TLC19 and N. calospora TLC9 have genome sizes of 46,4, 41,1 và 39,2 Mb, respectively, corresponding to 98,38%, 98,4% và 95,8% completeness.
S. commune TZT10, F. foetens AQF6 and F. solani TQF6 have genome sizes of 35,0 Mb; 39,4 Mb; 34,5 Mb, respectively, corresponding to > 96% completeness. 
Suggesting some metabolic pathways of endophytic fungal strains, including:
The podophylotoxin biosynthetic pathway in fungi is annotated on the KEGG database >35% including stage 1 genes encoding enzymes that convert phenylalanine to coniferyl alcohol and stage 2 genes encoding the bifunctional enzyme pinoresinol-lariciresinol reductase that produces pinoresinol and lariciresinol in the podophylotoxin pathway (from coniferyl alcohol to podophylotoxin).
The biosynthetic pathways of vinblastine and vincristine were constructed in the KEGG dataset. DDC and PRX1 are key protein-coding genes identified in three endophytic fungal strains Alternaria spp. DC1, Talaromyces spp. DC2, and Cladosporium spp. DC3 isolated from periwinkle plants.
Camptothecin biosynthetic pathway from genome sequencing and transcriptome analysis of Penicillium sp. I3R2 strain, including prediction of enzymes involved in the camptothecin biosynthetic pathway and expression levels of several genes encoding key enzymes in the camptothecin biosynthetic pathway.
Huperzine biosynthetic pathway from 3 fungal genomes
Paclitaxel biosynthesis pathway and decoding of secondary metabolite biosynthesis gene clusters from the fungal genome S. commune TZT10 carrying 4 genes related to paclitaxel biosynthesis (T13OH, T10OH, DBAT và BAPT); F. foetens AQF6 strain carrying 4 genes related to paclitaxel biosynthesis (TS, T13OH, T10OH và DBTNPT); F. solani TQF6 strain carrying 3 genes related to paclitaxel biosynthesis (T13OH, T10OH và DBTNPT).
Setting up 5 technological processes for biosynthesis fermentation of podophyllotoxin, vinblastine/vincristine, camptothecin, HupA and B, and paclitaxel at 70 liters/batch scale. The Host Unit officially recognized these processes after the Process Acceptance Councils approved them. 
Isolation and purification of compounds from fermentation liquid of endophytic fungal strains, including:
56 mg of podophyllotoxin compounds and derivatives contained in crude extracts from the fermentation broth of three strains of P. herquei HGN12C.1, P. citrinum HGN13C and F. proliferatum TQN5T.
97,5 mg vincristine and 61,5 mg vinblastine from fermentation broths of Alternaria spp. DC1, Talaromyces spp. DC2, and Cladosporium spp. DC3.
56 mg camptothecin extracted from Penicillium sp. I3R2.
74,6 mg HupB.
62 mg paclitaxel
3-12 mg other compounds: phenylacetic acid; p-hydroxybenzaldehyde; p-hydroxybenzeneacetic acid; salicylic acid; 2-hydroxybenzeneacetic acid; indole-3-acetic acid; β-adenosine; Cyclo-Leu-Leu; Cyclo-Pro-Val; N-[3-(methylthio)propyl]acetamide; N-phenethylacetamide.
- Purified compounds from P. citrinum HGN13C and F. proliferatum TQN5T strains all exhibited antioxidant and cytotoxic activities. Vincristine and vinblastine extracted from 3 endophytic fungal strains showed inhibitory effects on cancer cell lines A549, HeLa, HEPG2, MCF-7, SGC-7910, A2780, and K526. Similarly, purified camptothecin can inhibit over 90% at concentrations of 4 µg/mL on cancer cell lines A549, Sk-Lu-1, H23 with, and over 86% at concentrations of 4 µg/mL to colorectal cancer HT-29, SW480.
- Produce 8000 hard capsules containing Hup compound with an average content of ≥ 80 mcg/capsule and Cordyceps (content of 200 mg/capsule).
- Develop basic standards for capsules that are accepted by the Grassroots-level scientific council. The Institute of Biotechnology has decided to recognize the basic standards for safety reports on capsules and product declaration documents.
- Optimized the PRX1 gene sequence and constructed a recombinant vector pGreen3+HYG+PRX1 to express the PRX1 gene from periwinkle. Similarly, the SGD gene sequence from Penicillium sp. I3R2 strain was optimized and expressed in E. coli with the pET28TEV Erm vector.
In terms of application:
The project has produced several naturally occurring compounds with anti-cancer properties, including podophyllotoxin, vincristine, vinblastine, camptothecin, paclitaxel, and huperzine A and B. These compounds are highly sought after for their effectiveness in treating cancer, and their production is complex and costly. The project confirms that cancer drugs can be produced efficiently and safely. This production method also minimizes pressure on food safety and actively replaces dwindling supplies of medicinal plants. In addition, the application of modern biotechnology, sequencing the entire genome of selected fungal strains opens up strategies to impact their genomes, edit them to improve the synthesis efficiency of target compounds in the future. This is also one of the goals of exploiting and preserving the genetic resources of endogenous fungi of medicinal plants. At the same time, the product of hard capsules containing Hup compound combined with Cordyceps can support patients with memory loss.
Novelty and actuality and scientific meaningfulness of the results
- A total of 156 samples belong to 45 plant species were collected from many provinces and cities across the country, including many rare medicinal herbs that need to be preserved.
- Eight new compounds were detected such as wallichianone A, wallichianone B, taberbovinine A, taberbovinine B, iodescirrhoside A, iodescirrhoside B, iodescirrhoside C and iodescirrhoside D from Taxus wallichiana Zucc, Tabernaemontana bovina Lour, and Iodes cirrhosa Turcz samples.
- The project established a set of 1131 endophytic fungal strains, among them several strains can inhibit cancer cell lines and resist tested bacterial strains 
- Twenty-eight endophytic fungal strains were selected, of which 5 strains synthesized podophyllotoxin and its derivatives, 3 strains synthesized vincristine/vinblastine, 3 strains synthesized camptothecin, 14 strains synthesized HupA and/HupB, 3 strains synthesized paclitaxel or its derivatives. 
- Sequencing, assembling, and annotating the genomes of 15 endophytic fungal strains using PacBio technology and 01 transcript sequence of Penicillium sp. I3R2 strain, proposing 5 biosynthetic pathways of target compounds (podophylotoxin, vinblastine/vincristine, camptothecin, Huperzine, paclitaxel). The metabolic pathways in fungal cells closely resemble those in plants. 
- Five technological processes were developed for the biosynthesis fermentation of podophyllotoxin, vinblastine/vincristine, camptothecin, HupA & B, and paclitaxel at a scale of 70 liters per batch. 
- Produce 8000 hard capsules with an average content of ≥ 80 μg of Huperzine A compound and ≥ 200 mg of Cordyceps per capsule 
- The project optimized the sequences of key genes and isolated them from specific fungal strains to create recombinant vectors
Products of the project
Technology research and development products:
- 156 samples of 45 plant species were collected from many provinces in Vietnam, including Dysosma difformis, Dysosma versipellis, Catharanthus roseus L. (G.) Don, Oldenlandia corymbosa L., Ehretia asperula Zoll. et Mot., Scutellaria barbata D. Don, Crinum latifolium L., Callisia fragrans, Iodes sp., Iodes cirrhosa Turcz., Piper betle, Ixora chinensis, Ophiorrhiza japonica, Ophiorrhiza mungos, Ophiorrhiza baviensis, Lycopodiella cernua (L.) Pic. Serm., Lycopodium casuarinoides Spring., Lycopodium clavatum L., Lycopodium clavatum L., Huperzia serrata (Thunb.) Trevis., Huperzia javanica (Sw.) C. Yang., Phlegmariurus phlegmaria (L.) T.Sen & U.Sen, Phlegmariurus squarrosus (G. Forst.) Á.Löve & D.Löve, Phlegmariurus hamiltonii (Spreng.) Á.Löve & D.Löve, Phlegmariurus fordii (Baker) Ching, Phlegmariurus henryi (Baker) Ching, Amentotaxus ynnanensis H.L.Li, Taxus chinensis (Pilg.) Rehder, Cephalotaxus mannii Hook.f., Tsuga chinensis (Franch.) Pritz., Taxus wallichiana Zucc., Rhizophoraceae mucronata Lam, Kandelia obovata Sheue, H.Y.Liu & J.Yong, Bruguiera gymnorrhiza (L.) Savigny, Avicennia marina var. rumphiana (Hall. f.) Bakh), Aegiceras corniculatum (L.) Blanco, Taxus wallichiana Zucc., Tabernaemontana bovina Lour., Gomphandra tonkinesis Gagnep., Juniperus chinensis L., Podocarpus macrophyllus (Thunb.) Sweet, Tabernaemontana corymbosa Roxb. Ex Wall, Tabernaemontana langbianensis (Lý), Tabernaemontana divaricata (L.) R.Br. ex Roem. & Schult), Lycopodium clavatum L. Among these, 128 samples were fixed as specimens for storage
- 05 detailed reports on isolation and interpretation of chemical structure determination of compounds from medicinal plant samples: Taxus wallichiana Zucc., Tabernaemontana bovina Lour., Iodes cirrhosa Turcz., Gomphandra tonkinesis Gagnep., Juniperus chinensis L. (attach with NMR spectral data set)
- 01 detailed report on the results of evaluating the anti-cancer cell activity of the extracts and pure compounds from Taxus wallichiana Zucc., Tabernaemontana bovina Lour., Iodes cirrhosa Turcz., Gomphandra tonkinesis Gagnep., and Juniperus chinensis L.
- 01 detailed report on the outcome of antimicrobial activity testing of pure compounds isolated from Iodes cirrhosa Turcz.
- A set of 1131 endophytic fungal strains 
- 05 collections of strains producing podophyllotoxin and its derivatives; vincristine/vinblastine; camptothecin; HupA/HupB; and paclitaxel or its derivatives 
- 15 genomes of endophytic fungal strains using PacBio technology and 01 transcriptome of Penicillium sp. I3R2 strain 
- 05 schematic diagrams of the metabolic pathway in endophytic fungal strains, namely the podophyllotoxin biosynthetic pathway, the vinblastine and vincristine biosynthetic pathway, the camptothecin biosynthetic pathway, the Huperzine biosynthetic pathway, and the paclitaxel biosynthetic pathway.
- 05 biosynthetic fermentation process of podophyllotoxin, vinblastine/vincristine, camptothecin, HupA & B, and paclitaxel at a 70 liters/batch scale. 
- 62 compounds obtained from endophytic fungal strains with 80-90% purity (according to HPLC method), particullary: substance/precursor podophyllotoxin (56 mg); vincristine (97.5 mg); vinblastine (61.5 mg); camptothecin (56 mg); HupB (74.6 mg); Paclitaxel (62 mg); 3-12 mg of 11 other substances (phenylacetic acid; p-hydroxybenzaldehyde; p-hydroxybenzeneacetic acid; salicylic acid; 2-hydroxybenzeneacetic acid; indole-3-acetic acid; β-adenosine; Cyclo-Leu-Leu; Cyclo-Pro-Val; N-[3-(methylthio)propyl]acetamide; N-phenethylacetamide); ~ 2 mg/pure substance of 59 compounds in fungal samples isolated from Taxus wallichiana Zucc., Tabernaemontana bovina Lour., Iodes cirrhosa Turcz., Gomphandra tonkinesis Gagnep., and Juniperus chinensis L.
- 03 detailed reports on the biological activity of podophyllotoxin compounds and precursors such as α-Peltatin, β-Peltatin-5-O-β-D-glucopyranoside, Podophyllotoxin 4-O-glucoside, 2-(4-Hydroxyphenyl)ethanol, α-Peltatin-5-O-β-D-glucopyranoside, Scleroderolide; Vincristine and vinblastine; camptothecin.
- 8000 hard capsules with an average content of ≥ 80 μg of Huperzine A compound and ≥ 200 mg of Cordyceps per capsule 
- 01 basic standards for capsules that are accepted by the Grassroots-level scientific council, and have a decision of recognition 
- 01 safety analysis report for the capsule
- 01 capsule product declaration dossier
- 02 recombinant vectors: pGreen3+HYG+PRX1 expressing PRX1 gene and pET28TEV Erm expressing SGD gene.
10.2 Published scientific products:
- International publications:
Thi Tran H, Thu Nguyen G, Thi Nguyen HH, Thi Tran H, Hong Tran Q, Ho Tran Q, Thi Ninh N, Tien Do P, Hoang Chu H, Bich Pham N. Isolation and Cytotoxic Potency of Endophytic Fungi Associated with Dysosma difformis, a Study for the Novel Resources of Podophyllotoxin. Mycobiology. 2022. 50(5): 389-398.
Nguyen GT, Nguyen HTH, Tran HT, Tran HT, Ho AN, Tran QH, Pham NB. Enhanced podophyllotoxin production of endophyte Fusarium proliferatum TQN5T by host extract and phenylalanine. Appl Microbiol Biotechnol. 2023. 107(17): 5367-5378.
Nguyen DH, Tran QH, Le LT, Nguyen HHT, Tran HT, Do TP, Ho AN, Tran QH, Thu HTN, Bui VN, Chu HH, Pham NB. Genomic characterization and identification of candidate genes for putative podophyllotoxin biosynthesis pathway in Penicillium herquei HGN12.1C. Microb Biotechnol. 2024. 17(9): e70007.
Hoang NH, Huyen NT, Trang DT, Canh NX, Mao CV, Sopjani M, Vuong NB, Xuan NT. Effects of Vinblastine and Vincristine on the function of chronic myeloid leukemic cells through expression of A20 and CYLD. Cell Mol Biol. 2022. 68(10): 47-53. 
Nguyen DQ, Nguyen NL, Nguyen VT, Nguyen THG, Do TTT, Nguyen TH, Dung DH, Nguyen TKL, Nguyen QH, Le TT, and Nguyen HH. Isolation and identification of vincristine and vinblastine producing endophytic fungi from Catharanthus roseus (L.) G. Don. Russ J Plant Physio. 2023. 70: 188-198
Quan ND, Nguyen N-L, Giang TTH, Ngan NTT, Hien NT, Tung NV, Trang NHT, Lien NTK, Nguyen HH. Genome Characteristics of the Endophytic Fungus Talaromyces sp. DC2 Isolated from Catharanthus roseus (L.) G. Don. J Fungi. 2024. 10: 352.
Pham HM, Le DT, Le LT, Chu PTM, Tran LH, Pham TT, Nguyen HM, Luu TT, Hoang H, Chu HH. A highly quality genome sequence of Penicillium oxalium species isolated from the root of Ixora chinensis in Vietnam. G3 (Bethesda). 2023. 13(2): jkac300.
Doan TN, Le TD, Ho NA, Ho TT, Do TT, Hoang H, Nguyen MH, Bui TM, Chu HH. Isolation, anticancer potency, and camptothecin-producing ability of endophytic fungi isolated from Ixora chinensis. Sci Prog. 2024. 107(2): 368504241253675.
Le TTM, Pham HT, Trinh HTT, Tran HT, Chu HH. Isolation and Characterization of Novel Huperzine-Producing Endophytic Fungi from Lycopodiaceae Species. J Fungi (Basel). 2023. 9(12): 1134.
Le TTM, Pham HT, Trinh HTT. Quach TN, Do TT, Phi TQ, Chu HH. Huperzia javanica as a Novel Source of Huperzine Alkaloids and Huperzine-producing Fungi. Indian J Microbiol. 2024. Publish online 29/7/2024.
Vu THN, Pham NS, Le PC, Pham QA, Quach NT, Nguyen VT, Do TT, Chu HH, Phi QT. Distribution, cytotoxicity, and antioxidant activity of fungal endophytes isolated from Tsuga chinensis (Franch.) Pritz in Ha Giang province, Vietnam. Ann Microbiol. 2022. 72(36): 1-12. 
Vu THN, Quach NT, Le PC, Pham QA, Do TT, Chu HH, and Phi QT. Bioprospecting Endophytic Fungi Isolated from Cephalotaxus mannii Hook.f. as Prolific Sources of Antibacterial, Anticancer, and Antioxidant Agents. Microbiology. 2023. 92 (2): 284-292.
Vu THN, Pham NS, Quach NT, Le PC, Pham QA, Ngo CC, Nguyen VT, Anh DH, Quang TH, Chu HH, Phi QT. Fusarium foetens AQF6 Isolated from Amentotaxus ynnanensis H.L.Li as a Prolific Source of Antioxidant Compounds. 2024. Appl Sci. 14: 2048.
Ngoc NT, Quang TH, Quan NH, Hanh TTH, Cuong NX, Thanh NV, Ha CH, Nam NH, Minh CV. Cytotoxic monoterpenoid indole alkaloids from the leaves and twigs of Tabernaemontana bovina. Phytochem Lett. 2022. 51: 18-22.
Ngoc NT, Quang TH, Hanh TTH, Cuong NX, Cuong NT, Ha CH., Nam NH, Minh CV. Phenolic Glycosides from the Leaves of Iodes cirrhosa Turcz. with Cytotoxic and Antimicrobial Effects. Chem Biodivers. 2022. 19(9): e202200182.
Ngoc NT., Cuong DV, Hanh TTH, Cuong NX, Nam NH, Ha CH, Quang TH. Cytotoxic terpenoids from the stem bark of Taxus wallichiana. Phytochem Lett. 2022: 52, 113-117.
Le TTM, Trinh HTT, Pham HT, Nguyen DT, Do GH, Phan HT, Le TD, Quach NT, Phi TQ, Chu HH. Lycopodiaceae herb from Vietnam as a promising medicinal source of natural hupezine and novel huperzine-producing endophytic fungi. Gửi đăng 11/2023, sửa phản biện 8/2024 tại Tạp chí Biotechnol Lett.
Doan TN, Quach NT, Nguyen MH, Le TL, Ho NA, Hoang H, Chu HH. Genome-guided insights into endophytic lifestyle of Diaporthe ampelina I2T2. Đã gửi đăng trên Tạp chí Journal of Fungi.
- National publications:
Hoa TT, Thu Giang N, Hong Ha, NT, Huyen TT, Tien Phat D, Hoang Ha C, Bich Ngoc P, Ho Quang. T. Diversity of endophytic fungi from medicinal plants Dysosma difformis (Hemsl & E.H. Wilson) T.H. Wang collected in Ha Giang and Lai Chau. Vietnam Journal of Biotechnology. 2023. 21(2): 365–373.
Giang TTH., Quan ND, Linh DA, Lan NN, Huy LQ, Lien NTK, Hoang NH. Isolation and identification of endophytic fungi from Catharanthus roseus and Scutallaria barbata. Acad J Biol. 2021. 43(2): 1–10. 
Thuy CTT, Ngoc NTB, Quan ND, Thanh LT, Hoang NH, Hue HTT. Producing a recombinant vector that carries the vascular class III peroxidase (PRX1) gene from Catharanthus roseus. Acad J Biol. 2023. 45(4): 1–10.
Quach Ngoc Tung, Nguyen Mau Hung, Ho Ngoc Anh, Doan Thi Nhung, Hoang Ha, Chu Hoang Ha. Identification and characterization of endophytic fungi isolated from Ixora chinensis as potent source of antibacterial and anticancer agents. Chấp nhận đăng trên Tạp chí Vietnam Journal of Biotechnology. 2024.
Nguyen Mau Hung, Quach Ngoc Tung, Ho Ngoc Anh, Doan Thi Nhung, Hoang Ha, Chu Hoang Ha. Isolation and characterization of endophytic fungi isolated from Ophiorrhiza baviensis as a source of potential anticancer and antioxidant compounds. Chấp nhận đăng trên Tạp chí Vietnam Journal of Biotechnology. 2024.
Phạm Thanh Hà, Trịnh Thị Thu Hà, Phạm Thị Thoan, Đào Thị Hồng Vân, Lê Thị Minh Thành. Hoạt tính sinh học của một số chủng vi nấm nội sinh phân lập từ cây dược liệu họ thông đất Việt Nam. Tạp chí Khoa học Trường đại học Mở Hà Nội. 2023. 109: 46-56 
Nguyễn Thị Thảo, Đỗ Thị Tuyên, Phạm Thanh Hà, Trịnh Thị Thu Hà, Lê Thị Minh Thành. Nghiên cứu chiết xuất và tinh sạch huperzine B từ sinh khối lên men chủng nấm nội sinh cây dược liệu Thông đất. Tạp chí Công thương. 2024. 1: 42-46. 
Trịnh Thị Thu Hà, Phạm Thanh Hà, Hoàng Thị Yến, Lê Thị Minh Thành. Nghiên cứu hoạt tính sinh học của vi nấm nội sinh trên cây thạch tùng javanica (Huperzia javanica). Tạp chí Môi trường. 2024. 1: 52-57.
Quach Ngoc Tung, Vu Thi Hanh Nguyen, Le Phuong Chi, Tran Hong Quang, Do Thi Thao, Chu Hoang Ha, Phi Quyet Tien (2022). Fusarium fujikuroi WQF5 isolated from Cephalotaxus mannii Hook.f. as a producer of antibacterial agent and paclitaxel. Acad J Biol. 2022. 44(4): 53-63. 
Quach Ngoc Tung, Vu Thi Hanh Nguyen, Pham Quynh Anh, Tran Hong Quang, Chu Hoang Ha, Phi Quyet Tien. Screening and characterization of paclitaxel-producing fungus Talaromyces wortmannii WQF18 isolated from Cephalotaxus mannii Hook. f. Acad J Biol. 2023. 45(1): 77-85.
Ninh Thi Ngoc, Nguyen Viet Phong, Tran Hong Quang, Dang Viet Cuong, Tran Thi Hong Hanh, Nguyen Xuan Cuong, Chu Hoang Ha, Nguyen Hoai Nam. Diterpenes from the sterm bark of Taxus wallichiana Zucc. and their cytotoxic activity. Journal of Medicinal Materials. 2023. 28(2): 67-72.
- National Conference/ Workshop:
Trần Thị Hoa, Nguyễn Thị Hồng Hà, Nguyễn Thu Giang, Trần Hồ Quang, Đỗ Tiến Phát, Chu Hoàng Hà, Phạm Bích Ngọc. Khảo sát hoạt tính kháng khuẩn của chiết xuất vi nấm nội sinh HGN12.1R phân lập từ cây dược liệu Bát giác liên (Dysosma difformis) (Hemsl & E.H. Wilson) T.H. Wang). Báo cáo Kỷ yếu Hội nghị Công nghệ sinh học toàn quốc 10/ 2023. 540-543 (ISBN, 978-604-357-176-9).
Nguyễn Thị Hồng Hà, Trần Thị Hoa, Nguyễn Thị Thu Hiền, Phạm Bích Ngọc, Trần Hồ Quang. Phân lập và nghiên cứu đặc điểm sinh học của một số chủng vi nấm nội sinh trong Bát Giác Liên (Dysosma versipellis). Báo cáo Kỷ yếu Hội nghị Công nghệ sinh học toàn quốc 10/ 2023. 904-908 (ISBN, 978-604-357-176-9).
Trần Thị Hương Giang, Nguyễn Đức Quân, Nguyễn Thị Kim Liên, Nguyễn Thu Hiền và Nguyễn Huy Hoàng. Khai thác vi nấm nội sinh có tiềm năng sinh các hợp chất có dược tính sinh học từ cây dừa cạn (Catharanthus roseus) và một số cây dược liệu khác tại Việt Nam. Kỷ yếu hội thảo Quốc gia - Ứng dụng công nghệ sinh học trong chế biến, bảo quản và phát triển thực phẩm bảo vệ sức khỏe con người. 2021. Trường Đại học Mở Hà Nội.
Nguyễn Mậu Hưng, Quách Ngọc Tùng, Hồ Ngọc Anh, Đoàn Thị Nhung, Đỗ Thị Thảo, Hoàng Hà, Chu Hoàng Hà. Đánh giá hoạt tính gây độc tế bào ung thư và chống oxy hóa của vi nấm nội sinh phân lập trên cây xà căn (Ophiorrhiza baviensis Drake). Báo cáo Kỷ yếu Hội nghị Công nghệ sinh học toàn quốc 2024. (ISBN: 978-604-489-393-8).
Vũ Thị Hạnh Nguyên, Phạm Ngọc Sơn, Quách Ngọc Tùng, Phạm Quỳnh Anh, Lê Phương Chi, Nguyễn Văn Thế, Đỗ Thị Thảo, Phí Quyết Tiến. Phân loại và đánh giá hoạt tính sinh học của chủng vi nấm WQF7 nội sinh trên cây đỉnh tùng (Cephalotaxus mannii Hook.F.) tại Hà Giang. Báo cáo Kỷ yếu Hội nghị Công nghệ sinh học toàn quốc 2022. 424-429 (ISBN: 987-604-357-052-6).
Phạm Ngọc Sơn, Vũ Thị Hạnh Nguyên, Lê Phương Chi, Phạm Quỳnh Anh, Quách Ngọc Tùng, Lê Thị Thanh Xuân, Nguyễn Thị Thanh Lợi, Phí Quyết Tiến. Phân loại, đặc tính sinh học của chủng Penicillium crustosum WQF11 nội sinh trên cây đỉnh tùng (Cephalotaxus mannii Hook.F.). Báo cáo Kỷ yếu Hội nghị Công nghệ sinh học toàn quốc 2022. 430-435 (ISBN: 987-604-357-052-6).
Vũ Thị Hạnh Nguyên, Phạm Quỳnh Anh, Quách Ngọc Tùng, Phạm Ngọc Sơn, Nguyễn Việt Cường, Phí Quyết Tiến. Phân loại và nghiên cứu hoạt tính chống oxy hóa, gây độc tế bào ung thư của chủng Fusarium foetens TDF7 nội sinh trên cây thông đỏ bắc (Taxus chinensis). Báo cáo Kỷ yếu Hội nghị Công nghệ sinh học toàn quốc 2024: 254-259 (ISBN: 978-604-489-393-8).
Intellectual property:
- Invention:
“Chủng vi nấm Phoma sp. TKH3-2 thuần khiết về mặt sinh học có khả năng sinh tổng hợp hoạt chất huperzin A và huperzine B”. The application has been accepted as a valid application with No. 01-2022-02078 on 20/5/2022 
“Chủng vi nấm Phyllosticta sp. HG2-27  thuần khiết về mặt sinh học có khả năng sinh tổng hợp hoạt chất huperzin A và huperzine B”. The application has been accepted as a valid application with No. 01-2022-02079 on 02/6/2022
Chủng vi nấm nội sinh Aspergillus fumigatus SDF8 thuần khiết về mặt sinh học có hoạt tính gây độc tế bào ung thư và sinh tổng hợp chất chống oxy hóa. The application has been accepted as a valid application in 06/2022
“Chủng vi nấm nội sinh Fusarium foetens AQF6 thuần khiết về mặt sinh học có khả năng sinh tổng hợp các hoạt chất chống oxy hóa”. Patent No. 42313, issued on 09/12/2024.
- Utility solution:
“Chủng vi nấm Penicillium herquei HGN12.1C thuần khiết về mặt sinh học có khả năng sinh tổng hợp hoạt chất Podophyllotoxin”. Patent No. 3352, issued on 5/9/2023
“Chủng vi nấm Penicillium citrinum HGN13C thuần khiết về mặt sinh học có khả năng sinh tổng hợp hoạt chất Podophyllotoxin”. Patent No. 3355, issued on 6/9/2023
“Chủng vi nấm Fusarium proliferatum H11 thuần khiết về mặt sinh học có khả năng sinh tổng hợp hoạt chất podophyllotoxin”. Patent No. 3401, issued on 1/11/2023
“Chủng nấm Alternaria sp. DC1 thuần khiết về mặt sinh học”. The application has been accepted as a valid application according to Decision No. 97605/QD-SHTT on 13/11/2023
“Chủng nấm Talaromyces sp. DC2 thuần khiết về mặt sinh học”. The application has been accepted as a valid application according to Decision No. 97607/QĐ-SHTT on 13/11/2023
“Chủng vi nấm Penicillium sp. I3R2 thuần khiết về mặt sinh học có khả năng sinh tổng hợp hoạt chất camptothecin”. The application has been accepted as a valid application according to Decision No. 11334w/QĐ-SHTT on 06/07/2022
“Chủng vi nấm Epicoccum sorghinum THG01-18 thuần khiết về mặt sinh học có khả năng sinh tổng hợp hoạt chất huperzin A và huperzine B”. The application has been accepted as a valid application with No. 02-2022-00056 on 28/02/2022.
“Chủng vi nấm Daldinia sp. TLC-19 thuần khiết về mặt sinh học có khả năng sinh tổng hợp hoạt chất huperzin A”. The application has been accepted as a valid application with No. 02-2022-00057 on 28/02/2022 
“Chủng vi nấm Schizophyllum commune TLC-12 thuần khiết về mặt sinh học có khả năng sinh tổng hợp hoạt chất huperzin A”. The application has been accepted as a valid application with No. 02-2022-00134 on 20/5/2022 
“Chủng vi nấm Aspergillus sp. TTĐ2-2.7 thuần khiết về mặt sinh học có khả năng sinh tổng hợp hoạt chất huperzin A”. The application has been accepted as a valid application with No. 02-2022-00135 on 20/5/2022
“Chủng vi nấm nội sinh Penicillium crustosum WQF11 thuần khiết về mặt sinh học có khả năng sinh tổng hợp hoạt chất paclitaxel”. Patent No. 3666, issued on 08/8/2024.
Postgraduated training:
- Master of Science: 05
- Supporting for PhD’ course: 02