title: Mucor fragilis as a novel source of the key pharmaceutical agents podophyllotoxin and kaempferol.
abstract: BACKGROUND
  Podophyllotoxin, a pharmaceutically important bioactive compound of Podophyllum sps. (Berberidaceae), is in great demand worldwide as an anticancer and antivirus drug precursor. However, the source of podophyllotoxin is very limited due to the endangered status of the Podophyllum plant.
  
  
  OBJECTIVE
  The aim of this study was to isolate podophyllotoxin-producing endophytic fungi from Sinopodophyllum hexandrum (Royle) Ying (1979) (Berberidaceae) plants of the Taibai Mountains of China in order to obtain bioactive compounds.
  
  
  METHODS
  The strains producing kaempferol and podophyllotoxin were screened by thin-layer chromatography (TLC) analysis. The presence of kaempferol and podophyllotoxin in extracts of these strains was further confirmed by high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR) analyses.
  
  
  RESULTS
  Among six endophytic fungi isolated from the rhizomes of S. hexandrum, one strain was able to produce kaempferol. Another strain, named TW5, was able to produce both kaempferol and podophyllotoxin simultaneously according to the TLC, HPLC, and NMR results. The podophyllotoxin yield of TW5 was calculated to be 49.3 μg/g of mycelial dry weight after 7-d fermentation. Strain TW5 was identified morphologically and phylogenetically to be Mucor fragilis Fresen. (Mucoraceae). These results suggest that the podophyllotoxin-synthesizing ability is obtained by uptaking genes involved in the podophyllotoxin synthesis from the host plant into endophytic fungal genomes.
  
  
  CONCLUSIONS
  Our results showed, for the first time, that the endophytic fungus M. fragilis is able to produce simultaneously the same two bioactive metabolites, podophyllotoxin and kaempferol, as its host plant. Furthermore, the relatively high podophyllotoxin yield obtained may improve the industrial production of podophyllotoxin, which may help protect this endangered plant.
authors.affiliation: College of Life Science, Northwest University, Xi'an, China .
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiao-Rui
authors.initials: XR
authors.lastname: Zhang
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiao-Rui
authors.initials: XR
authors.lastname: He
mesh_terms: D002855:Chromatography, Thin Layer / Q000379:methods; D044949:Kaempferols / Q000032:analysis* / Q000737:chemistry; D009089:Mucor; D011034:Podophyllotoxin / Q000032:analysis* / Q000737:chemistry; D027343:Rhizome
chemical_list: D044949:Kaempferols; C006552:kaempferol; D011034:Podophyllotoxin
keywords: High performance liquid chromatography; Sinopodophyllum hexandrum; endophytic fungus; nuclear magnetic resonance; podophyllotoxin