title: Biotransformation of metoprolol by the fungus Cunninghamella blakesleeana.
abstract: OBJECTIVE
  To investigate the biotransformation of metoprolol, a beta1-cardioselective adrenoceptor antagonist, by filamentous fungus, and to compare the parallels between microbial transformation and mammalian metabolism.
  
  
  METHODS
  Five strains of Cunninghamella (C elegans AS 3.156, C elegans AS 3.2028, C echinulata AS 3.2004, C blakesleeana AS 3.153 and AS 3.910) were screened for the ability to transform metoprolol. The metabolites of metoprolol produced by C blakesleeana AS 3.153 were separated and assayed by liquid chromatography-tandem mass spectrometry (LC/MS(n)). The major metabolites were isolated by semipreparative HPLC and the structures were identified by a combination of LC/MS(n) and nuclear magnetic resonance analysis.
  
  
  RESULTS
  Metoprolol was transformed to 7 metabolites; 2 were identified as new metabolites and 5 were known metabolites in mammals.
  
  
  CONCLUSIONS
  The microbial transformation of metoprolol was similar to the metabolism in mammals. The fungi belonging to Cunninghamella species could be used as complementary models for predicting in vivo metabolism and producing quantities of metabolite references for drugs like metoprolol.
authors.affiliation: Center for Drug Metabolism and Pharmacokinetics Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Ma
authors.forename: Hai-hua
authors.initials: HH
authors.lastname: Huang
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Chen
authors.forename: Yu-ming
authors.initials: YM
authors.lastname: Sun
authors.forename: Li-hong
authors.initials: LH
authors.lastname: Lin
authors.forename: Da-fang
authors.initials: DF
authors.lastname: Zhong
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D020093:Cunninghamella / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D008790:Metoprolol / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure
chemical_list: D000319:Adrenergic beta-Antagonists; D008790:Metoprolol