Open Access Peer-reviewed Research Article

Microbial synthesis of anti-tumor agent oxysophoridine through one step by filamentous fungus

Article Sidebar

Biosynthesis of OSR by microbial strains
Download PDF Download HTML
Submitted   Apr 6, 2019
Published   May 9, 2019
Issue    Vol 1 No 2 (2019)
DOI   10.25082/JPBR.2019.02.001

Views

2786

Downloads

2313

Citations

PlumX Metrics

Main Article Content

Qingfeng Meng
Department of Public Health, Zunyi Medical University, Zunyi, 563000, China
Xuan Zhou
Department of Pharmacy, Zunyi Medical University, Zunyi, 563000, China; Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, Zunyi, 563000, China
Xu Ran
Department of Pharmacy, Zunyi Medical University, Zunyi, 563000, China
Song Yan
Department of Pharmacy, Zunyi Medical University, Zunyi, 563000, China
Shaobin Fu corresponding author
Department of Pharmacy, Zunyi Medical University, Zunyi, 563000, China; Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, Zunyi, 563000, China

Abstract

Sophoridine and oxysophoridine are alkaloids extracted from Chinese traditional medicine with significant antitumor activities. Computer-aided design and preliminary structure-activity relationship studies showed that the biological activity of sophoridine can be improved after oxidation (oxysophoridine) while its toxicity significantly decreased. A new method to prepare oxysophoridine from natural product Sophoridine by biotransformation was established for the first time except for traditional extraction from plants and chemical synthesis.  Positive biocatalytic reaction was detected by TLC. Structure of conversion product was elucidated based on NMR spectroscopy. Optimizations of reactions including substrate concentration, pH, conversion time and inoculation quantity were complemented which analyzed by LC-MS. Results showed that filamentous fungus Xylariales. sp F005 (CCTCC M2014660) has the capacity of synthetizing oxysophoridine from sophoridine in the selected 37 strains. The yield of oxysophoridine reached highest at conditions pH 6.0, the third day of conversion time, 5.0 mg substrate and 5% inoculums respectively. The method for preparing oxysophoridine catalyzed by enzymes with green and sustainable synthetic processes was developed.

Keywords
biotransformation, alkaloid, fungus, natural product, condition optimization

Article Details

Supporting Agencies
The National Natural Sciences Foundation of China (21462057), Guizhou Science and Technology Department (QKHLH-2014-7555), Training Programs of Innovation and Entrepreneurship for Undergraduates (Zunyi Medical University 20163742), National First-Rate Construction Discipline of Guizhou Province. (Pharmacy) (YLXKJS-YX-04), the Fifth Batch of Talent Base in Guizhou Province (2016)
How to Cite
Meng, Q., Zhou, X., Ran, X., Yan, S., & Fu, S. (2019). Microbial synthesis of anti-tumor agent oxysophoridine through one step by filamentous fungus. Journal of Pharmaceutical and Biopharmaceutical Research, 1(2), 48-52. https://doi.org/10.25082/JPBR.2019.02.001
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

References

  1. Rothenberg ML. Topoisomerase I inhibitors：Review and update．Annals of Oncology, 1997, 8: 837-855. https://doi.org/10.1023/A:1008270717294
  2. Li XM, Wu YG, Pan DX, et al. sophoridine is a new antitumor medicine with new molecular structure. Chinese Journal of New Drugs, 2006, 1: 654-657.
  3. Ren G, Ding GT, Zhang HY, et al. Antiviral activity of sophoridine against enterovirus 71 in vitro. Journal of Ethnopharmacology, 2019, 236: 124-128. https://doi.org/10.1016/j.jep.2019.02.045
  4. Dai LL, Li DD, Zhao XM, et al. Synthesis and Antitumor Effect of Sophoridine Derivatives Bearing an Acyclic Aryloxy Phosphoramidate Mustard Functionality. Journal of Heterocyclic Chemistry, 2019, 56(2): 417-425. https://doi.org/10.1002/jhet.3413
  5. Wang WX, Sun ZH, Chen HM, et al. Role and mechanism of Sophoridine on proliferation inhibition in human glioma U87MG cell line. International Journal of Clinical & Experiment medicine, 2015, 8: 464-671.
  6. Liu J, Liu Y, Li B, et al. Sophoridine suppresses inflammatory cytokine secretion by lipopolysaccharide-induced RAW264.7 cells and its mechanism. Chinese Journal of Cellular and Molecular Immunology, 2015, 31: 585-589.
  7. Hong G and Liu PX. Study on Chemical constituent & anti-tumor activity of a novel drug SPRIDA, 2005.
  8. Liu P and Yu LH. The application of oxymatrine in the preparation of anticancer drugs, N1739510 patent, 2006.
  9. Wang YS, Li YX, Zhao P, et al. Anti-inflammation Effects of Oxysophoridine on Cerebral Ischemia-Reperfusion Injury in Mice. Inflammation, 2015, 8: 2259-2268. https://doi.org/10.1007/s10753-015-0211-4
  10. Cao Z, Chen L, Liu YB, et al. Oxysophoridine rescues spinal cord injury via anti-​inflammatory, anti-​oxidative stress and anti-​apoptosis effects. Molecular Medicine Reports, 2018, 17(2): 2523-2528. https://doi.org/10.3892/mmr.2017.8170
  11. Wang TF, Lei Z, Li YX, et al. Oxysophoridine protects against focal cerebral ischemic injury by inhibiting oxidative stress and apoptosis in mice. Neurochemical Research, 2013, 38: 2408-2417. https://doi.org/10.1007/s11064-013-1153-6
  12. Jin SJ, Yang Y, Ma BH, et al. In vivo and in vitro induction of the apoptotic effects of oxysophoridine on colorectal cancer cells via the Bcl‑2/Bax/caspase-3 signaling pathway. Oncology Letter, 2017, 14: 8000-8006. https://doi.org/10.3892/ol.2017.7227
  13. Dong JZ, Yi ZL and Jiang JX. Current situation of the Research on the Germ Plasm Resources of Medicinal plant in china. Journal of West China Forestry Science, 2005, 34: 95-100.
  14. Hegazy ME, Mohamed TA, Elshamy AI, et al. Microbial biotransformation as a tool for drug development based on natural products from mevalonic acid pathway: A review. Journal of Advanced Research, 2015, 6: 17-33. https://doi.org/10.1016/j.jare.2014.11.009
  15. Xu SH, Zhang C, Wang WW, et al. Site-selective biotransformation of ursane triterpenes by Streptomyces griseus ATCC 13273. RSC Advances, 2017, 7(34): 20754-20759. https://doi.org/10.1039/C7RA01811H
  16. Guan ZH, Li XG, Wang L, et al. Conversion of Tibetan grasslands to croplands decreases accumulation of microbially synthesized compounds in soil. Soil Biology & Biochemistry, 2018, 123: 10-20. https://doi.org/10.1016/j.soilbio.2018.04.023
  17. Pfister CA and Altabet MA. Enhanced microbial nitrogen transformations in association with macrobiota from the rocky intertidal. Biogeosciences, 2019, 16(2): 193-206. https://doi.org/10.5194/bg-16-193-2019
  18. Fu S, Li Y, Meng Q, et al. Regio-selective Reduction of Oxysophoridine by Microorganism Isolated from Soil. Journal of the Chinese Chemical Society, 2016, 63(4): 331-335. https://doi.org/10.1002/jccs.201500501